SEARCH · PubMed Health

Results for “ARTERIOSCLEROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1982

[Immune pathogenesis models of arteriosclerosis (author's transl)].

Immune pathogenesis models of arteriosclerosis can be divided in 2 groups: autoaggression and allergy models. Particular relevance is admitted to the effect of immune complexes as these can release a large part of the basic mechanisms of arteriosclerosis. Whether and in which extent immune mechanisms approach a causal role to the human arteriosclerosis in fact still isn't, decided absolutely. Possible immunologic causes must be seen always in connection with already assured pathogenesis models and risk factors of arteriosclerosis. In proved immune mechanisms it must be clarified whether they are result, amplifying factor or cause of the arteriosclerosis. It could be made very probably that immune reactions could be a sequence or amplifying factor of arteriosclerosis. Whether they play also a causal role in the spontaneous arteriosclerosis requires further investigations.

Antigen-Antibody Complex↗

PubMed1997

Accelerated arteriosclerosis after transplantation: the possible role of calcium channel blockers.

The major factor limiting the long-term success of cardiac transplantation is the development of accelerated arteriosclerosis that occurs in the coronary arteries of the cardiac allograft. Transplant arteriosclerosis is characterized by diffuse, uniform, concentric narrowing of the artery by a proliferative, fibrocellular intima. The etiology of transplant arteriosclerosis is thought to be immune-mediated, and endothelial cells, smooth muscle cells, and inflammatory cells participate in the progression. Based on data derived from studies of conventional atherosclerosis, in which calcium channel blockers (CCBs) have demonstrated beneficial effects, preliminary studies designed to determine if CCBs might affect transplant arteriosclerosis similarly have been performed in animal models as well as in a limited number of cardiac transplant patients. Amlodipine suppressed transplant arteriosclerosis in one animal study, while diltiazem preserved vasodilatory responses in another animal study. Small prospective trials and retrospective studies in humans have shown that CCBs have a favorable effect on the development of transplant arteriosclerosis. While no work has been directed specifically at determining the mechanisms by which CCBs might prevent transplant arteriosclerosis, there are several likely candidates. These include preservation of endothelial function, suppression of smooth muscle cell migration and proliferation, production of extracellular matrix, and regulation of lipid metabolism and certain components of the immune system.

Amlodipine↗

PubMed1989

Inhibition of accelerated cardiac allograft arteriosclerosis by fish oil.

Accelerated coronary arteriosclerosis remains the most important factor limiting long-term survival of heart transplant recipients, and dietary fish oil supplementation with omega-3 polyunsaturated fatty acids has been suggested to have a protective effect against coronary disease in epidemiologic studies and to inhibit arteriosclerosis in animal experiments. Therefore we tested the hypothesis that fish oil administration inhibits the development of allograft coronary arteriosclerosis by using a heterotopic heart transplant model. Three groups of Lewis rats (n = 10 each) received heterotopic heart transplants from Brown-Norway donors and were treated with cyclosporine intraperitoneally on a tapering schedule. Group 1 received fish oil daily by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona, N.Y.). Group 2 received an equal amount of safflower oil, as well as aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received safflower oil only. All rats were put to death 110 days later, at which time there was no statistically significant difference in graft function as assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard deviation]; analysis of variance: p = 0.72) or in microscopic grade of rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of variance: p = 0.68) between any of the groups. The coronary arteries were histologically scored for the degree of arteriosclerosis (scale, 0 = normal to 3 = occluded), and a mean grade of coronary disease was calculated for each heart. The fish oil-treated group had significantly less severe allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96 +/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had similar degrees of coronary disease (p = no significant difference). These data demonstrate that fish oil supplementation inhibited accelerated coronary arteriosclerosis in this cyclosporine-treated heart allograft rat model, whereas antiplatelet agents in these doses were ineffective. Although the mechanism of this protective effect remains incompletely understood, it does not appear to involve enhanced immunosuppression. Fish oil and specific omega-3 polyunsaturated fatty acids should be further investigated as potentially useful agents to ameliorate accelerated allograft coronary arteriosclerosis in other animal species and perhaps eventually in man.

Animals↗

PubMed2001

[The site and extent of arteriosclerosis. Comparative planimetric studies of the left descending coronary artery, internal carotid artery, superficial femoral artery and abdominal aorta in 104 cadavers].

BACKGROUND: Arteriosclerosis is generally considered to be a generalized disease, involving different vascular regions to approximately the same extent. PATIENTS AND METHODS: In order to assess the extent of ateriosclerosis quantitatively, all arteriosclerotic lesions and additionally the complicated (calcified, ulcerated, thrombosed) arteriosclerotic lesions of the abdominal aorta, the superficial femoral arteries, the left descending coronary artery and the internal carotid arteries were measured by planimetry in 102 autopsies (64 male, 38 female; mean age: 62 +/- 16 years). RESULTS: Arteriosclerosis increased with age. The overall extent of arteriosclerotic lesions of each artery was classified to one of the following 4 degrees of intimal involvement (0-25, 26-50, 51-75%, 76-100%). When comparing the 4 different vascular regions of each patient we found maximal deviations by 1 degree in 34%, by 2 degrees in 41% and by 3 degrees in 20%. In only 5% of the patients studied were all arteriosclerotic lesions of the same degree. In order to analyze the complicated plaques 7 degrees were used (intimal involvement: 0, 1-10, 11-20, 21-30, 31-40, 41-50% and > 50%). In 14 patients we found no complicated plaques. The remaining 88 showed complicated lesions in at least 1 vascular region. Deviations by 1 degree were found in 22%, by 2 degrees in 32%, and by 3 or more degrees in 46%. In the paired arteries (carotid, femoral) there were no significant differences comparing the mean values of the extent of arteriosclerotic lesions on the right and left side. In many cases, however, remarkable intraindividual differences occurred. Patients with main risk factors usually had more pronounced arteriosclerotic lesions than those without. In patients who died from coronary artery disease the extent of arteriosclerotic lesions was also usually larger in the other vascular regions as compared to those patients who died from other reasons. Comparing postmortem and intravital extent of arteriosclerotic lesions some peculiarities of postmortem specimens should be considered. CONCLUSIONS: A uniform involvement of all vascular regions by arteriosclerosis occurs only rarely. Considerable intraindividual differences are the rule and a severe, generalized uniform affection is an exception. This, however, does not exclude in patients with severe arteriosclerosis of one region that a larger involvement of other vascular regions may also occur, as this was found for patients with severe arteriosclerosis in coronary arteries. Regarding the extent of arteriosclerosis there are artery- and additional localization-specific features.

Adult↗

PubMed2004

Association between pentosidine and arteriosclerosis in patients receiving hemodialysis.

BACKGROUND: It has been suggested that advanced glycation endproducts (AGEs) accumulate in arteriosclerotic lesions, playing and important role in the development and progression of arteriosclerosis. A chemical quantification method using high-performance liquid chromatography (HPLC) has been established to determine pentosidine levels in these products. Some studies reported that the abdominal aorta calcification index (ACI), obtained by computed tomography (CT), was useful for noninvasively diagnosing arteriosclerosis and determining its severity. In the present study, we measured the ACI and plasma pentosidine in patients receiving maintenance hemodialysis, and investigated the association between arteriosclerosis and pentosidine. METHODS: In 73 patients receiving maintenance hemodialysis (43 men; 30 women), we determined the ACI, and investigated the association of the ACI with plasma total pentosidine, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, serum creatinine, and parathyroid hormone (PTH), as well as the product of serum calcium and serum phosphorus, duration of dialysis, and age. RESULTS: The ACI did not correlate with total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, serum creatinine, PTH, or the product of serum calcium and serum phosphorus. Age, duration of dialysis, and plasma total pentosidine correlated with the ACI: (y = -33.12 + 0.913x; r = 0.407; P < 0.01), (y = 13.94 + 0.403x; r = 0.488; P < 0.01), and (y = 14.13 + 0.630x; r = 0.365; P < 0.01), respectively. CONCLUSIONS: It is suggested that pentosidine may be associated with arteriosclerotic development in hemodialysis patients. It has been suggested that advanced glycation endproducts (AGEs) accumulate in arteriosclerotic lesions, playing an important role in the development and progression of arteriosclerosis. A chemical quantification method using high-performance liquid chromatography (HPLC) has been established to determine pentosidine levels in these products. Some studies reported that the abdominal aorta calcification index (ACI), obtained by computed tomography (CT), was useful for noninvasively diagnosing arteriosclerosis and determining its severity. In the present study, we measured the ACI and plasma pentosidine in patients receiving maintenance hemodialysis, and investigated the association between arteriosclerosis and pentosidine.

Aged↗

PubMed2004

Mouse models of arteriosclerosis: from arterial injuries to vascular grafts.

Animal models are designed to be preliminary tools for better understanding of the pathogenesis, improvement in diagnosis, prevention, and therapy of arteriosclerosis in humans. Attracted by the well-defined genetic systems, a number of investigators have begun to use the mouse as an experimental system for arteriosclerosis research. Hundreds of inbred lines have been established, and the genetic map is relatively well defined, and both congenic strains and recombinant strains are available to facilitate genetic experimentation. Because arteriosclerosis is a complicated disease, which includes spontaneous (native) atherosclerosis, transplant arteriosclerosis, vein graft atherosclerosis, and angioplasty-induced restenosis, several mouse models for studying all types of arteriosclerosis have recently been established. Using these mouse models, much knowledge concerning the pathogenesis of the disease and therapeutic intervention has been gained, eg, origins of endothelial and smooth muscle cells in lesions of transplant and vein graft atherosclerosis. This review will not attempt to cover all aspects of mouse models, rather focus on models of arterial injuries, vein grafts, and transplant arteriosclerosis, by which the major progress in understanding the mechanisms of the disease has been made. This article will also point out (dis)advantages of a variety of models, and how the models can be appropriately chosen for different purposes of study.

Animals↗

PubMed2002

Levels of haemostatic factors, arteriosclerosis and cardiovascular disease.

Plasma levels of haemostasis factors (HFs) such as fibrinogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer may be markers of arteriosclerosis for the following reasons: There seems to be no difference in levels of HFs between patients with longstanding stable angina and those with an isolated myocardial infarction. HF levels are generally positively associated with subclinical arteriosclerosis as determined by ankle-arm index and carotid ultrasonography in asymptomatic individuals. Levels of most HFs are positively associated with inflammation, which is an essential part of the initiation and progression of the disease. A rough classification is assigned to the associations found in under (2) and (3). Fibrinogen is strongly associated with subclinical arteriosclerosis and with inflammation; Factor VII is not, while an intermediate group is formed by, for instance, von Willebrand Factor (vWF), Factor VIII (F VIII), t-PA, PAI-1, and D-dimer. Also, the associations of HFs with cardiovascular events follow a similar pattern. Fibrinogen is a strong and consistent risk factor in several studies, Factor VII is not, and a similar intermediate group as mentioned under (2) and (3) exists. It suggests that the risk of cardiovascular events in relation to HF levels is explained by their identity as markers of arteriosclerosis. A causal association between HF levels and the disease is not proven. Out of the HF, the markers of coagulation such as thrombin-antithrombin complex and of fibrinolysis such as D-dimer are more likely to act causally. Increased levels indicate that they are markers of arteriosclerosis, but in addition, they may reflect a low-grade, continuous formation and subsequent lysis of fibrin in the disease. As the latter reflects an increased tendency to thrombosis, a causal association of levels of markers of coagulation and fibrinolysis with arteriosclerosis, although not yet proven, seems likely.

Animals↗

PubMed2000

Parameters for the preoperative evaluation of arteriosclerosis for free-flap transfers in head and neck surgery.

The microsurgical transfer of free tissue has become essential for reconstructive surgery in the head and neck, and arteriosclerosis is one of the risk factors for microvascular anastomosis. In order to detect severe arteriosclerosis and to determine the parameters useful for evaluating arteriosclerosis preoperatively, the grade of arteriosclerosis was investigated with respect to age, PWV (Aortic Pulse Wave Velocity), ocular fundus findings, and histopathological findings of the recipient arteries in 40 patients with malignant tumours. Severe arteriosclerosis was detected in 2/40 patients by the PWV, in the same 2/40 patients by the ocular fundus findings and in the same 2/40 patients by histopathological findings. The current observations indicate that the PWV and ocular fundus findings are useful parameters for the preoperative evaluation of the grade of arteriosclerosis.

Adult↗

PubMed1995

Relative importance of ischemic injury and immunological injury on the development of transplant arteriosclerosis in rabbit aortic allografts.

The development of transplant arteriosclerosis has emerged as a major problem to long-term survival after heart transplantation. The accelerated development of arteriosclerosis in the transplanted arteries, including the aorta, could result either from an ischemic injury in connection with the transplantation, or from an immunological reaction against the transplant, or both. We evaluated histologically and biochemically whether extension of the ischemic period from 1 to 24 hr has any influence on the development of transplant arteriosclerosis, in aorta-allografted rabbits clamped at human levels of plasma cholesterol. One set of rabbits was without immunosuppressive treatment (n = 10 + 9) and another otherwise identical set of rabbits received cyclosporine to achieve blood cyclosporine levels in the human therapeutic range (n = 10 + 12). The number of T lymphocytes in intima suggested that, in the grafts from untreated animals, an immunological injury had arisen, which cyclosporine reduced. A clear trend toward a worsening of the transplant arteriosclerosis was demonstrated as a function of the severity of the ischemic injury, both with and without immunosuppressive treatment. However, the worsening effect of maximal ischemic injury was less than that due to maximal immunological injury. In grafts from cyclosporine-treated animals, the development of transplant arteriosclerosis was significantly less than in grafts from untreated animals exposed to identical periods of ischemia. These results suggest that compared with immunological injury, ischemic injury is of minor importance for the development of experimental transplant arteriosclerosis.

Animals↗

PubMed1997

Inducible nitric oxide synthase suppresses the development of allograft arteriosclerosis.

In cardiac transplantation, chronic rejection takes the form of an occlusive vasculopathy. The mechanism underlying this disorder remains unclear. The purpose of this study was to investigate the role nitric oxide (NO) may play in the development of allograft arteriosclerosis. Rat aortic allografts from ACI donors to Wistar Furth recipients with a strong genetic disparity in both major and minor histocompatibility antigens were used for transplantation. Allografts collected at 28 d were found to have significant increases in both inducible NO synthase (iNOS) mRNA and protein as well as in intimal thickness when compared with isografts. Inhibiting NO production with an iNOS inhibitor increased the intimal thickening by 57.2%, indicating that NO suppresses the development of allograft arteriosclerosis. Next, we evaluated the effect of cyclosporine (CsA) on iNOS expression and allograft arteriosclerosis. CsA (10 mg/kg/d) suppressed the expression of iNOS in response to balloon-induced aortic injury. Similarly, CsA inhibited iNOS expression in the aortic allografts, associated with a 65% increase in intimal thickening. Finally, we investigated the effect of adenoviral-mediated iNOS gene transfer on allograft arteriosclerosis. Transduction with iNOS using an adenoviral vector suppressed completely the development of allograft arteriosclerosis in both untreated recipients and recipients treated with CsA. These results suggest that the early immune-mediated upregulation in iNOS expression partially protects aortic allografts from the development of allograft arteriosclerosis, and that iNOS gene transfer strategies may prove useful in preventing the development of this otherwise untreatable disease process.

Animals↗

PubMed2005

Hyperhomocysteinemia and arteriosclerosis: historical perspectives.

Early concepts of the origin of arteriosclerosis were introduced in the 19th century by Rokitansky and Virchow, who described mural thrombosis, inflammatory damage to arterial intima, increased intimal permeability to plasma, mucoid degeneration of arterial wall, deposition of plasma lipids in plaques, and fibrosis and calcification of plaques. Experimental production of arteriosclerosis by feeding animal foods to rabbits was attributed to protein intoxication by Ignatowsky in 1908 and to dietary cholesterol by Anitschkow in 1913. Newburgh confirmed the protein hypothesis in 1915-1925 but failed to identify which amino acid produced plaques because methionine (1922) and homocysteine (1932) had not yet been discovered. Cases of homocystinuria from inherited deficiency of cystathionine synthase were found to be associated with thrombosis and vascular disease in 1964. The index case of methionine synthase deficiency (cobalamin C disease) was found by McCully in 1969 to be associated with arteriosclerosis, leading to the homocysteine theory of arteriosclerosis. The theory explains experimental arteriosclerosis by deficiency of vitamin B6 in monkeys, choline deficiency in rats, thyroid deficiency in rats, and methionine deficiency in monkeys. The thrombogenic and atherogenic effects of homocysteine were demonstrated in rabbits, baboons and other species, reproducing the pathological findings found in homocystinuria. Clinical and epidemiological studies in the past two decades have demonstrated that elevated plasma homocysteine is a potent independent risk factor for arteriosclerosis in the general population, supporting the validity of the theory.

Animals↗

PubMed1990

Accelerated arteriosclerosis in heart transplant recipients is associated with a T-lymphocyte-mediated endothelialitis.

Accelerated arteriosclerosis has emerged as a major life-threatening complication in long-term survivors of heart transplantation. It has been proposed that accelerated arteriosclerosis is an immune-mediated complication of rejection. We observed a striking endothelialitis in the coronary arteries of two explanted hearts obtained from patients with severe transplant-related accelerated arteriosclerosis. This finding prompted us to review the pathologic changes in the coronary arteries of 23 autopsied patients who had received heart transplants. The infiltrate in these vessels was characterized using immunohistochemical stains for lymphocytes (CD45), macrophages (MAC-387), T lymphocytes (CD45RO), B lymphocytes (L-26), and smooth muscle cells (actin). In addition, a full panel of monoclonal antibodies was used on the fresh-frozen tissue available from one of the two explanted hearts. Ten of the eleven recipients with accelerated arteriosclerosis had a moderate to marked lymphocytic endothelialitis compared to 3 of 14 without transplant-related arteriosclerosis (P less than 0.005). Immunohistochemical staining of the paraffin-embedded material demonstrated that most of the lymphocytes in the subendothelial space of these vessels were T lymphocytes and that this infiltrate was associated with an accumulation of macrophages and a proliferation of smooth muscle cells in the intima. In the explanted heart from which fresh-frozen tissue was available for more detailed cell typing, the T cells marked predominantly as cytotoxic T lymphocytes (CD8+, CD2+). These results suggest that accelerated arteriosclerosis may be mediated, in part, by a cytotoxic T-lymphocyte-directed endothelialitis.

Adult↗

PubMed1992

Myocardial changes in cardiac transplant-associated coronary arteriosclerosis: potential for timely diagnosis.

Graft arteriosclerosis is the major limitation to long-term survival after heart transplantation. In this study, myocardial pathologic changes, especially those that might permit early diagnosis, were characterized in endomyocardial biopsy specimens and hearts obtained at retransplantation or autopsy from nine orthotopic heart transplant recipients. All had severe diffuse proliferative arterial stenoses without plaque rupture or coronary thrombi. Eight patients died with and one underwent retransplantation because of graft arteriosclerosis less than 12 months (six patients) or greater than 46 months (three patients) after operation. Six patients had antecedent symptoms of congestive heart failure and six had angiographically demonstrated epicardial coronary artery graft arteriosclerosis; four had both. Myocardial ischemic lesions included subendocardial myocyte vacuolization (seven patients) and microfocal to regional coagulation necrosis and granulation tissue or scar, or both (seven patients). Subendocardial myocyte vacuolization (indicative of sublethal ischemic injury) was diagnosed at prior right ventricular biopsy in two patients and was noted at autopsy in areas accessible to right-sided biopsy in three additional patients. Three patients had pathologic changes diagnostic of acute infarction on right or left ventricular biopsy, or both. Thus, all nine patients had lesions, of which five had biopsy-identified myocardial abnormalities caused by graft arteriosclerosis. It is concluded that graft arteriosclerosis yields not only myocardial pathologic changes similar to those associated with typical coronary atherosclerosis, but also lesions resulting from focal or diffuse ischemia caused by small vessel obstructions. This is manifest as subendocardial myocyte vacuolization or microfocal infarction. Recognition of these biopsy-accessible myocardial changes associated with graft arteriosclerosis may allow early recognition and appropriate therapeutic intervention.

Acute Disease↗

PubMed2000

Development of a combined cardiac and aortic transplant model to investigate the development of transplant arteriosclerosis in the mouse.

BACKGROUND: The degree of transplant arteriosclerosis in murine cardiac allografts is difficult to assess. Aortic allografts represent an alternative model for evaluating the impact of novel transplant strategies on transplant arteriosclerosis in which the vascular changes can be quantified easily. However, it remains controversial as to whether vascular lesions seen in this model are equivalent to those that develop in solid-organ transplants. The aim of this study was to develop a model of combined cardiac and aortic transplantation to allow more precise quantification of transplant arteriosclerosis and to establish a correlation between the lesions that develop in the 2 types of graft. METHODS: CBA (H2(k)) recipients received a C57BL/10 (H2(b)) cervical cardiac allograft on Day 0 and a C57BL/10 (H2(b)) abdominal aortic allograft on Day 1. Recipients were treated with anti-CD154 mAb (MR1) on Days 0, 2, and 4. We performed histology and morphometric measurements for both grafts 30 days after transplantation. RESULTS: We observed significant intimal proliferation in both the cervical cardiac and abdominal aortic allografts from recipients treated with anti-CD154 mAb (heart, 64% +/- 9%; aorta, 67% +/- 8%; n = 5). Abdominal aortic grafts transplanted alone into anti-CD154-treated recipients developed a degree of transplant arteriosclerosis equivalent to that seen in the aortic grafts of the combined group (aorta alone, 68% +/- 9%, vs aorta + heart, 67% +/- 8%; n = 5). CONCLUSIONS: This combined cardiac and aortic transplant model permitted quantitative assessment of transplant arteriosclerosis while monitoring graft survival by cardiac palpation. Furthermore, development of transplant arteriosclerosis was equivalent in abdominal aortic allografts either in the presence or absence of an additional solid- organ transplant.

Animals↗

PubMed2001

Metabolism of hepatocyte growth factor in the heart in patients with coronary artery disease: implication for coronary arteriosclerosis.

PURPOSE: HGF, one of endothelium-specific growth factors, might contribute to the repair process of vascular endothelial cell damage, suggesting that serum HGF concentration may be elevated in patients with arteriosclerosis. However, the cardiac metabolism of HGF has not been examined in patients with coronary artery disease (CAD). We examined the levels of hepatocyte growth factor (HGF) in the coronary circulation and its correlation with the severity of arteriosclerosis in patients with CAD. METHODS: We measured serum HGF concentration obtained from the coronary sinus (CS) and ascending aorta (AA) in patients with atherosclerotic CAD (Group E, n = 33) or vasospastic angina (Group V, n = 26), or normal control subjects (Group N, n = 12). In Group E, the severity of coronary artery stenosis was evaluated using the Gensini's score. RESULTS: Serum HGF concentrations (ng ml) in the CS were 0.112 +/- 0.008 in Group E (p < 0.001 vs. Group V, p < 0.001 vs. Group N), 0.197 +/- 0.012 in Group V (p = 0.031 vs. Group N), and 0.245 +/- 0.021 in Group N. Serum HGF concentrations in the AA were 0.282 +/- 0.014 in Group E (p = 0.045 vs. Group V, p = 0.021 vs. Group N), 0.246 +/- 0.012 in Group V, and 0.237 +/- 0.009 in Group N. Serum HGF extraction in the heart (HGF in the AA-HGF in the CS) in Group E (0.170 +/- 0.018) was significantly higher compared with in Group V (0.049 +/- 0.011) or Group N (0.008 +/- 0.005). There was a significant negative correlation between the severity of coronary arteriosclerosis and serum HGF concentration in CS (r = -0.66, p < 0.001), and a significant positive correlation between the severity of coronary arteriosclerosis and HGF extraction in the heart (r = 0.75. p < 0.001). CONCLUSIONS: We conclude that the difference of HGF levels between CS and AA in patients with CAD are decreased, and extent of decreases in HGF levels correlates with the severity of coronary arteriosclerosis. The abnormality of HGF metabolism in the heart may contribute to the progression of coronary arteriosclerosis.

Case-Control Studies↗

PubMed1996

Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft.

Cardiac allograft arteriosclerosis is the most important limiting factor of long-term survival of heart transplant recipients. Several clinical studies have suggested the association between CMV infection and heart allograft arteriosclerosis, chronic rejection. To determine the temporal impact of CMV infection on the development of heart allograft arteriosclerosis we quantitated coronary angiograms obtained from 72 heart transplant recipients followed for 1-6 yr post-transplantation. To examine the graft function, echocardiography was evaluated. CMV infection was associated with early development of allograft arteriosclerosis manifested by intense diffuse pruning of the coronary arteries including their smallest branches already after the second post-transplant year. Even 6 yr post-transplantation the magnitude of arteriosclerotic changes was significantly higher in recipients with CMV infection compared with patients without infection (P < 0.02). No difference in echocardiographic parameters including ejection fraction (EF), left ventricular end diastolic diameter (LVEDD) and left ventricular mass (LVM) between recipients with and without CMV infection was recorded early after transplantation. However, when compared to recipients without CMV, the CMV accelerated chronic rejection seen in coronary angiography associated with impaired late graft function as judged by decreased EF in patients with CMV infection 6 yr post-transplantation (P < 0.02). No differences in LVEDD or LVM between the patient groups occurred. Taken together, these results suggest that CMV infection is associated with intense cardiac allograft arteriosclerosis affecting the whole coronary tree soon after transplantation. The intensity and magnitude of these chronic vascular wall changes increase and persist during subsequent years, indicating that the risk for graft loss and death due to chronic rejection is especially high during the first 5 post-transplant years in CMV-infected patients. Echocardiography may not be a sensitive method to distinguish patients with early CMV-accelerated allograft arteriosclerosis but coronary angiography must be performed.

Acute Disease↗

PubMed1994

Role of calcium antagonists in progression of arteriosclerosis. Evidence from animal experiments and clinical experience. Part I. Preventive effects of calcium antagonists in animal experiments.

The quantitative predominance of free and total cholesterol over the amount of mural calcium is a most significant criterion of healthy human coronary arteries during the whole life span (0-90 years). However, this normal ratio increasingly changes as soon as arteriosclerotic alterations of the coronary walls set in. Accordingly, the mural calcium content steadily rises from fatty streaks over severe arteriosclerosis and, lastly, seems to reach a climax in plaques which caused lethal coronary infarction. Furthermore, the severe arteriosclerosis of human art. dorsalis pedis with gangrene (and amputation) is characterized by a tremendous calcium incorporation and absence of any mural cholesterol changes. Only in rare cases of human basilary plaques was a dangerous cholesterol incorporation in brain arterial wall found without significant elevation of serum cholesterol levels. The presented data indicate the existence of two different types of arteriosclerosis in one and the same patient and two basically different types of experimental coronary plaques according to their chemical composition, microscopic aspect and responsiveness to calcium antagonists: 1) the calcium type, developing in vitamin-D3-treated rats, and 2) the cholesterol type, represented by fatty coronary atheromata of cholesterol-fed rabbits. Coronary atheromata of cholesterol-fed New Zealand rabbits may be suitable models for coronary heart disease in rare cases of human familiar hypercholesterolemia. The formation of conventional human coronary artery plaques, however, essentially requires a progressive uptake of calcium, thereby representing a calcium dominated type of arteriosclerosis. Calcium antagonists specifically inhibit progredient mural calcium uptake in all experimental models of arteriosclerosis tested so far. However, neither in atheromatous arteries nor in afflicted organs (myocardium, liver, kidneys) of cholesterol-fed rabbits were we able to find any significant prevention of cholesterol accumulation by calcium antagonist.

Aging↗

PubMed1993

A pathohistological and biochemical study of arteriosclerosis in the internal thoracic artery, a vessel commonly used as a graft in coronary artery bypass surgery.

Pathohistological and biochemical studies were conducted on the severity of arteriosclerosis in the internal thoracic artery (ITA), an artery commonly used for coronary artery bypass grafting (CABG). For the pathohistological examination, 26 bilateral ITAs and 13 left anterior descending coronary arteries (LADs) obtained in full length from 13 autopsy cases, none of which had died of arteriosclerotic heart disease, were used. The ratio of the thickness of the intima to that of the media (R) was used as the index for arteriosclerosis. ITAs and LADs were classified as grades I to IV according to the value of R. The R of the ITAs was approximately 1/10 that of the LADs (P < 0.01). Most ITAs showed a low arteriosclerotic grade, with no variation in arteriosclerosis along their length and a low R in all segments. No difference was found between right and left ITAs. Biochemical examination was conducted on 12 ITAs and 11 LADs, obtained from 12 different and unselected autopsy cases. The lipid content in the vascular wall was determined to evaluate the severity of arteriosclerosis, with the following results: Total cholesterol, 5.5 +/- 1.8 and 17.8 +/- 13.6 micrograms/mg wet weight (P < 0.05); triglyceride, 90.4 +/- 90.3 and 114.4 +/- 117.2 micrograms/mg wet weight (n.s.); and phospholipid, 7.4 +/- 3.9 and 11.2 +/- 3.9 micrograms/mg wet weight (P < 0.05), respectively, for the ITAs and LADs. These findings thus demonstrate that arteriosclerosis of the ITA in Japanese people is very mild, compared to that of the LAD in the same individuals.

Adult↗