Biomedical subjects

A Lerman

Publications and source records attributed to A Lerman.

At least 19 recordsLinked to original sources

PubMed2000

Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

BACKGROUND: Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. METHODS AND RESULTS: Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. CONCLUSIONS: Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

Acetylcholine↗

PubMed2000

Activated nuclear factor-kappaB is present in the coronary vasculature in experimental hypercholesterolemia.

BACKGROUND: Experimental hypercholesterolemia (HC) is characterized by a decrease in nitric oxide (NO) bioavailability and cellular proliferation. Nuclear factor-kappaB (NF-kappaB) is a transcriptional factor which plays a coordinating role in inflammation and cellular proliferation and may be involved in early atherosclerosis. We examined whether activated NF-kappaB was present in experimental hypercholesterolemia in the coronary vasculature in association with a decrease in NO bioavailability. METHODS: A total of 14 juvenile domestic crossbred pigs were placed on a HC diet and six pigs on a normal diet for 10-12 weeks. A monoclonal antibody to the activated form of the p65 subunit of NF-kappaB was used to detect immunoreactivity in coronary artery sections. Coronary tissue homogenates were analyzed for activated NF-kappaB and endothelial nitric oxide synthase (eNOS) using Western blotting. In vitro coronary endothelium-dependent relaxation was performed in response to bradykinin, as a measure of NO bioavailability. RESULTS: Intimal staining for activated NF-kappaB was present in 12/14 HC pigs as compared with 0/6 controls (P<0.001). Confocal microscopy confirmed the presence of NF-kappaB in the nucleus of intimal cells although the majority of the staining was cytoplasmic. In the HC group, Western blotting revealed an increase in activated NF-kappaB in the vessel wall compared to the normal group, in association with a decrease in the presence of eNOS protein and an attenuated vasorelaxation response to bradykinin. CONCLUSION: This study suggests a potential role for activation of NF-kappaB, in association with a decrease in NO bioavailability, in the initial stages of atherosclerosis in the coronary vasculature.

Animals↗

PubMed2000

Natriuretic peptide levels in atrial fibrillation: a prospective hormonal and Doppler-echocardiographic study.

OBJECTIVES: The objective was to determine the independent association between atrial fibrillation (A-Fib) and activation of natriuretic peptides. BACKGROUND: The association of A-Fib with activation of N-terminal atrial and brain natriuretic peptides (N-ANPs and BNPs, respectively) is uncertain but of great importance for the diagnostic utilization of natriuretic peptides. This uncertainty is related to the lack of appropriate controls, with left ventricular (LV) and atrial overload similar to A-Fib. METHODS: We prospectively measured N-terminal atrial and BNPs and endothelin-1 levels in 100 patients and 14 age- and gender-matched control subjects. The 32 patients with A-Fib were compared with 68 patients in sinus rhythm and similar LV and atrial overload (due to mitral regurgitation or LV dysfunction) measured simultaneously with hormonal levels with comprehensive Doppler echocardiography. RESULTS: Patients with A-Fib compared with those in sinus rhythm had similar symptoms, comorbid conditions, cardioactive medications, pulmonary pressure, left atrial volume, and LV ejection fraction and filling characteristics but demonstrated higher N-ANP levels (2,613 +/- 1,681 vs. 1,654 +/- 1,323 pg/ml, p = 0.007) even after adjustment for the underlying cardiac disease (p < 0.0001). Conversely, BNP levels were similar in both groups (165 +/- 163 vs. 160 +/- 269 pg/ml, p = 0.9). In multivariate analysis, a higher N-ANP level was associated with A-Fib (p = 0.0003), symptom class (p < 0.0001) and endothelin-1 level (p = 0.032) independently of left atrial volume and LV ejection fraction. Conversely, BNP showed no independent association with and was most strongly associated with LV ejection fraction (p < 0.0001). CONCLUSIONS: Atrial fibrillation is an independent determinant of higher N-ANP levels and blurs its association with LV dysfunction. Conversely, the BNP is not independently associated with A-Fib and is strongly determined by LV dysfunction, for which it is an independent marker.

Aged↗

PubMed2000

Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy.

OBJECTIVES: The purpose of this study was to evaluate the association between hypertension and left ventricular hypertrophy (LVH) with both coronary vascular remodeling and endothelial function. BACKGROUND: The association between endothelial and nonendothelial coronary flow reserve with vascular remodeling in patients with hypertension and LVH is still unclear. METHODS: One hundred and eleven patients with normal or mildly diseased coronary arteries at angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Patients were divided into three groups: group 1: n = 13, hypertensive patients with LVH; group 2: n = 30, hypertensive patients without LVH; group 3: n = 68, normotensive patients. Vessel and lumen area and atherosclerotic plaque area were evaluated. Vascular reactivity was examined using intracoronary adenosine and acetylcholine. RESULTS: Vessel area in group 1 (with LVH) was significantly (p < 0.01) greater than that in group 2 (without LVH), whereas, vessel area in both groups 1 and 3 was similar (12.8 +/- 0.8 mm2, 10.7 +/- 0.4 mm2 and 11.5 +/- 0.3 mm2). Coronary blood flow at baseline for patients in group 1 (with LVH) was significantly greater than it was for patients in groups 2 and 3 (81.1 +/- 9.9 ml/min, 56.5 +/- 6.2 ml/min and 48.1 +/- 3.2 ml/min, both p < 0.05). In comparison with groups 2 and 3, the response to both acetylcholine and adenosine was significantly impaired in patients with LVH. CONCLUSIONS: The current study demonstrates that hypertension with LVH is associated with both coronary vascular remodeling and attenuated endothelial and nonendothelial coronary flow reserve.

Acetylcholine↗

PubMed2000

Endothelin in cardiovascular disease: from atherosclerosis to heart failure.

Since the discovery of endothelin (ET) as a potent vasoconstrictor, increasing evidence supports the role of ET in the pathogenesis of cardiovascular diseases including coronary artery disease and congestive heart failure. This peptide not only alters vascular tone and cardiac hemodynamics, but also has a substantial role in the regulation of cellular proliferation and apoptosis, activation of monocytes and cellular matrix production. Thus, ET may play a role in the pathogenesis of cardiovascular diseases through multiple mechanisms. The development of ET receptor antagonists has lead to a greater understanding of the role of the endogenous ET system in both physiologic and pathophysiologic states. Endothelin receptor antagonists are becoming new therapeutic tools for the treatment of cardiovascular disease and their study will lead to a greater understanding of the role of ET in disease progression.

Animals↗

PubMed2000

Insulin and insulin-like growth factor-I cause vasorelaxation in human vessels in vitro.

BACKGROUND: Insulin and insulin-like growth factor-I (IGF-I) are endogenous peptides with vasoactive activities. OBJECTIVE: To evaluate the vasodilatory effects of insulin and IGF-I on human vessels taken from patients with and without noninsulin-dependent diabetes mellitus (NIDDM) and to elucidate their mechanisms of action. METHODS: Vascular rings of human internal mammary artery (IMA) and saphenous vein harvested from 54 patients with and without NIDDM undergoing coronary bypass surgery were studied in vitro. RESULTS: For samples from patients without NIDDM both insulin and IGF-I (10(-12)-10(-7) mol/l) evoked greater relaxation in IMA rings (30 +/- 4 and 29 +/- 6%, maximal relaxation +/- SEM, respectively) than they did in saphenous-vein rings (43 +/- 4 and 42 +/- 5%, respectively, P < 0.05 both for insulin and for IGF-I). Similar results were obtained with vessels from patients with NIDDM. Relaxation was not affected by the removal of the endothelium and by inhibition of the production of nitric oxide. However, the vascular relaxation caused by insulin and IGF-I was completely abolished by KCI, and was attenuated by the nonspecific potassium-channel blocker tetraethylammonium (for IMA rings, to 77 +/- 8 and 66 +/- 4% with insulin and IGF-I, respectively; for saphenous vein rings, 73 +/- 2 and 77 +/- 1% for insulin and IGF-I, respectively, P < 0.001). CONCLUSIONS: Both insulin and IGF-I induced endothelial-independent, nitric oxide-independent vasorelaxation of rings from human IMA and saphenous veins, through a mechanism involving activation of potassium channels. This response remained intact in vessels from patients with NIDDM. This result supports the hypothesis that insulin and IGF-I play roles in the regulation of vascular tone in human vessels.

Diabetes Mellitus, Type 2↗

PubMed2000

Cholesterol-lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries.

Coronary vascular remodeling and altered endothelial function have been described in the early stages of native atherosclerosis. The purpose of this study was to evaluate the association between cholesterol-lowering therapy and coronary vascular remodeling and endothelial function in patients with normal or mildly diseases coronary arteries. Patients (N=101) with normal or mildly diseased coronary arteries by coronary angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Vessel and lumen area, atherosclerotic plaque area, and plaque morphology were evaluated. Vascular reactivity was examined with the use of intracoronary adenosine, acetylcholine, and nitroglycerin. Patients were divided into 3 groups based on the total cholesterol levels: group 1 (n=25), patients with a history of hypercholesterolemia adequately treated (total cholesterol <240 mg/dL); group 2 (n=26), patients with hypercholesterolemia not adequately controlled (total cholesterol >/=240 mg/dL); and group 3 (n=50), patients without hypercholesterolemia. Vessel area and lumen area were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: vessel area 11.9+/-0.5, 10.6+/-0.4, and 11.8+/-0.4 mm(2), both P<0.05; lumen area 8.3+/-0.4, 6.9+/-0.3, and 8.9+/-0.3 mm(2), both P<0.01). However, plaque areas in groups 1 and 2 were similar. Furthermore, acetylcholine-induced percent increases in coronary blood flow were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: 70.5+/-20.1%, 22.8+/-13.7%, and 68.6+/-14.8%, both P<0. 05). Cholesterol-lowering treatment is associated with an improvement in coronary lumen area that results not from a decrease in plaque area but from an increase in vessel area, reflecting vascular remodeling. Additionally, this adaptive process may occur in association with an improvement of endothelium-dependent vasodilation of the resistance coronary artery.

Anticholesteremic Agents↗

PubMed1999

Systemic amyloidosis presenting with angina pectoris.

BACKGROUND: Manifestations of cardiac amyloidosis may include congestive heart failure and sudden cardiac death. Although vascular involvement in patients with amyloidosis is common, systemic amyloidosis presenting with angina is rare. OBJECTIVES: To report on patients with systemic amyloidosis presenting with angina pectoris. DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Five patients who presented with angina pectoris and normal coronary angiogram as the initial manifestation of systemic amyloidosis. MEASUREMENTS: Endothelial-dependent and endothelial-independent coronary flow reserve. RESULTS: All patients had coronary flow reserve abnormalities and subsequently developed congestive heart failure and systemic manifestations of amyloidosis. Histologic evaluation revealed amyloid deposition in the intramyocardial coronary vessels. CONCLUSIONS: Cardiac amyloidosis can present as angina pectoris associated with coronary flow reserve abnormalities despite normal coronary angiograms. This finding may have major therapeutic and prognostic implications in this patient population.

Aged↗

PubMed1999

Measuring maximal percent area stenosis poststent placement with intracoronary Doppler and the continuity equation and correlation with intracoronary ultrasound and angiography.

Quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) are methods for anatomic assessment of stent deployment. Intracoronary Doppler is primarily a method for the physiologic assessment of coronary stenoses. It correlates well with traditional noninvasive measurements of lesion significance. Intracoronary Doppler was used for the anatomic assessment of de novo coronary artery stenosis with variable success; however, its use for anatomic assessment of adequate stent deployment is unavailable. A rapid, automated software program was developed based on a modified continuity equation to calculate the maximal in-stent percent area stenosis by comparing the maximal in-stent velocity to an average reference velocity (proximal and distal). This study was designed to compare the Doppler method of an anatomic assessment with QCA and ICUS in 15 patients. Physiologic success of stent deployment was determined by the distal coronary flow reserve to 24 to 36 microg of intracoronary adenosine. Following successful stent deployment, distal coronary flow reserve increased significantly from a baseline of 1.6 +/- 0.5 to 2.9 +/- 1.1. There was a significant correlation between the maximal in-stent percent area stenosis as measured by Doppler and both QCA (r = 0.78, p <0.01) and ICUS (r = 0.84, p <0.01). This study demonstrates that maximal in-stent percent area stenosis can be measured by intracoronary Doppler and a novel software program. The intracoronary Doppler guidewire method can assess the adequacy of stent deployment using both anatomic and physiologic principles and may supplement other quantitative methodologies.

Adenosine↗

PubMed1999

Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia.

BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived peptide that constricts coronary vessels through stimulation of the ET-A and ET-B receptors. Experimental porcine hypercholesterolemia is associated with impaired coronary endothelial function and elevated ET-1 concentrations. This study was designed to test the hypothesis that chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. METHODS AND RESULTS: Acetylcholine (10(-6) to 10(-4) mol/L) was serially infused into the left anterior descending coronary artery in pigs at baseline and after 12 weeks of a high-cholesterol diet. In the interim, the animals were randomized to 3 groups: Group 1 received no therapy, group 2 received 3 mg/kg per day RO 48-5695, a combined ET-A/ET-B receptor antagonist, and group 3 received 4 mg/kg per day ABT-627, a selective ET-A receptor antagonist. Percent change in coronary artery diameter, coronary blood flow, and coronary vascular resistance were calculated on the basis of quantitative coronary angiography and intracoronary Doppler. At 12 weeks, total cholesterol was significantly and similarly increased in all groups. Chronic endothelin receptor antagonism significantly increased coronary blood flow in response to acetylcholine at 12 weeks (group 1: -41.6%+/-10.7%, group 2: -4.7%+/-11.9%, group 3: 11.4%+/-7.4%). CONCLUSIONS: Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia. This study supports the role for ET-1 in the pathogenesis of endothelial function. Moreover, endothelin receptor antagonists may have a therapeutic role by maintaining coronary endothelial function in pathophysiological states.

Administration, Oral↗

PubMed1999

Medical therapy after successful percutaneous coronary revascularization.

BACKGROUND: Percutaneous coronary revascularization frequently relieves angina in patients with ischemic heart disease and may obviate the need for antianginal medications. OBJECTIVE: To examine the use of antianginal medications after successful percutaneous coronary revascularization. DESIGN: Retrospective cohort study of the Mayo Clinic PTCA [percutaneous transluminal coronary angioplasty] Registry. SETTING: Tertiary care center. PATIENTS: 3831 patients who underwent successful percutaneous coronary revascularization from September 1979 through August 1997 and had not had myocardial infarction within the year before the intervention. MEASUREMENTS: Use of antianginal medications (beta-adrenergic blockers, nitrates, and calcium-channel blockers) before the intervention, at hospital discharge, and 6 months after the intervention. RESULTS: 99% of patients reported improvement in their symptoms at hospital discharge. At 6 months, 87% of patients were free of myocardial infarction, coronary bypass surgery, or additional percutaneous intervention. Compared with 66% of patients before the index intervention, only 12% of patients had severe angina at 6 months and 69% were completely free of angina. Nonetheless, at 6 months, 39% of patients were receiving beta-adrenergic blockers (preprocedure proportion, 43%; P < 0.001), 36% were receiving nitrates (preprocedure proportion, 41%; P < 0.001), and 57% were receiving calcium-channel blockers (preprocedure proportion, 50%; P < 0.001). These trends persisted for patients without hypertension and those who had complete revascularization. CONCLUSIONS: Successful percutaneous coronary revascularization did not substantially supplant the use of antianginal medications, which were commonly used despite the marked improvement in anginal status. This may reflect reluctance to alter therapy once symptoms of angina subside. Guidelines on continued medical therapy after percutaneous coronary revascularization are needed.

Adrenergic beta-Antagonists↗

PubMed1999

Evaluation of microvascular anatomy by micro-CT.

Observations indicate that adventitial vasa vasorum may play a role in the development and/or the progression of coronary atherosclerosis. There is a lack of information regarding the spatial three-dimensional pattern of the vasa vasorum in the coronary artery. This is due to the technical difficulties in visualizing the course of this fine vascular network with histologic methods. Microscopic computed tomography (micro-CT) is a novel technique that allows three-dimensional views of the entire microvascular structure. The current review summarizes our current advances in using this technique in visualization of the coronary circulation.

Animals↗

PubMed1999

The assessment of endothelial function in the cardiac catheterization laboratory in patients with risk factors for atherosclerotic coronary artery disease.

In the last 2 decades the endothelium has emerged as an active modulator of many local and systemic functions. The intact endothelium synthesizes and releases a variety of autocrine and paracrine substances that affect cell growth and proliferation, platelet aggregation and adhesion, inflammatory processes, and vascular tone. The aims of the present review are to present the current technique for the assessment of coronary artery endothelial function in the cardiac catheterization laboratory and to describe the current knowledge regarding risk factor modification on endothelial dysfunction.

Animals↗

PubMed1999

Smoking status and outcome after primary coronary angioplasty for acute myocardial infarction.

BACKGROUND: Because of the increased propensity of intracoronary thrombi to form in cigarette smokers, percutaneous transluminal angioplasty (PTCA) for acute myocardial infarction (AMI) may be less effective in smokers. We sought to determine the impact of smoking status on outcome after PTCA for AMI. METHODS: Patients enrolled in the GUSTO IIb Angioplasty Substudy were randomly assigned to receive PTCA or tissue-plasminogen activator (tPA) for AMI. The interaction of smoking status (nonsmokers = 344, former smokers = 294, current smokers = 490) and treatment strategy with the occurrence of death, nonfatal reinfarction, or nonfatal, disabling stroke at 30 days was analyzed. Procedural success (residual stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) was also analyzed for patients who underwent PTCA (n = 444). RESULTS: Among patients who underwent PTCA, nonsmokers had worse percent stenosis of the culprit lesion before reperfusion (P =.03) and more often had TIMI flow grade 0 (P <.05). Procedural success was more common in smokers (65.6%) than in former smokers (53.3%) and nonsmokers (52. 4%; P =.02), reflecting a higher rate of postprocedure TIMI 3 flow. PTCA was associated with a better 30-day outcome than tPA for current smokers (odds ratio [95% confidence interval] = 0.41 [0.19 to 0.88]), with a similar trend for former smokers (0.73 [0.34 to 1. 58]) and nonsmokers (0.77 [0.42 to 1.40]). At 6 months, smokers randomly assigned to PTCA also had fewer deaths and reinfarction (0. 58 [0.31 to 1.07]). CONCLUSIONS: Although smoking status affects angiographic variables before and after PTCA for AMI, PTCA is associated with a better 30-day outcome than tPA regardless of smoking status and should be considered when readily available.

Angioplasty, Balloon, Coronary↗

PubMed1999

Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2 alpha, in experimental hypercholesterolemia.

OBJECTIVES: The F2-isoprostanes are a family of novel prostaglandin isomers and a stable product of in vivo oxidative stress. 8-epi-prostaglandinF2 alpha, a member of this isoprostane family, is a vasoconstrictor and its local release may contribute to the abnormal vasomotor tone associated with hypercholesterolemia. We therefore aimed to outline the role of 8-epi-prostaglandinF2 alpha as a coronary vasoconstrictor in experimental hypercholesterolemia. METHODS AND RESULTS: Pigs were randomized to two experimental groups (each n = 9): normal (N) and high cholesterol (HC) diet. To determine the vasoconstrictive effects of 8-epi-prostaglandinF2 alpha in vitro, doses from 10(-9) to 10(-5) M were used to constrict coronary epicardial rings. Plasma total and LDL cholesterol levels were significantly higher in the HC group compared with the N group (P < 0.005) as were plasma 8-epi-prostaglandinF2 alpha levels (P < 0.001). 8-epi-prostaglandinF2 alpha immunoreactivity was present in the vessel wall in both groups. Normal vessels with intact endothelium (n = 8 rings) contracted to 8-epi-prostaglandinF2 alpha (maximal contraction 15.5 +/- 8.74%). In the HC group, rings with intact endothelium had a greater contractile response to 8-epi-prostaglandinF2 alpha compared to normals (72.3 +/- 7.9%; n = 8; P < 0.0001). This was reversed by preincubation with NOR-3, a NO donor (maximal contraction 6.7 +/- 1.56%; n = 5; P < 0.0001). Enhanced contraction in normal vessels occurred with endothelial denudation (98.4 +/- 3.56%; n = 6; P < 0.0001) and with preincubation of the endothelium-intact rings with L-NMMA (N-monomethyl-L-arginine), an NO synthase inhibitor (85.5 +/- 10.3%, n = 6, P < 0.001). The enhanced contraction seen with hypercholesterolemia did not occur with other prostanoid vasoconstrictors. CONCLUSION: Experimental hypercholesterolemia leads to a significant increase in 8-epi-prostaglandinF2 alpha levels in addition to enhanced 8-epi-prostaglandinF2 alpha-induced coronary vasoconstriction, in vitro. These findings support a role for the F2-isoprostanes in the regulation of coronary vasomotor tone in pathophysiologic states.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

Coronary artery apoptosis in experimental hypercholesterolemia.

The altered coronary vasoactivity detected in experimental hypercholesterolemia before lesion formation is presumably due to an imbalance between vasodilating and vasoconstricting factors. Apoptosis, which has been previously described in advanced atherosclerosis, is modulated by vascular derived peptides with vasoactive properties. We hypothesized that coronary apoptosis occurs in experimental hypercholesterolemia prior to lesion formation. Pigs were sacrificed after being on either a high-cholesterol diet for 10-16 weeks (n = 17) or a normal diet (n = 9). Identification of apoptosis in each layer of coronary arteries and arterioles was performed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL). In additional animals, ligation-mediated polymerase chain reaction (PCR) and transmission electron and confocal microscopy were done. Plasma cholesterol levels were higher in the cholesterol-fed animals (86+/-9 mg/dl versus 342+/-20 mg/dl, P < 0.001). Atheromatous plaques were not evident in the high-cholesterol group. TUNEL was positive in 11 of 17 hypercholesterolemic animals, primarily in the intima (1-2% of cells) and adventitia (3% of cells), but not in control vessels. A similar distribution was detected in arterioles. DNA bands were detected only in experimental animals, as were morphological features of apoptosis by transmission electron and confocal microscopy. In experimental hypercholesterolemia, apoptosis occurred in coronary arteries and arterioles before lesion formation. Apoptosis may be an integral process of early coronary atherosclerosis.

Animals↗

PubMed1999

Apoptosis. Basic concepts and implications in coronary artery disease.

Apoptosis is an active form of cell death that is intricately regulated and distinct from necrosis. Data suggest that apoptosis may play a role in the pathophysiology of coronary atherosclerotic disease. Anatomic evidence of apoptosis has been observed in coronary atherosclerosis, restenosis, and transplant arteriopathy, accompanied by an increase in biochemical and genetic markers of apoptosis. Vasoactive substances such as nitric oxide and angiotensin II also regulate vascular smooth muscle cell apoptosis; vasodilating factors may induce apoptosis, whereas vasoconstricting factors may inhibit apoptosis. The aim of this article is to review key points regarding the detection of apoptosis, its regulation, and its possible role in the pathogenesis of coronary artery disease.

Apoptosis↗

PubMed1999

Coronary endothelial function is preserved with chronic endothelin receptor antagonism in experimental hypercholesterolemia in vitro.

Hypercholesterolemia is associated with increased circulating and tissue endothelin-1 immunoreactivity, decreased nitric oxide (NO) activity, and altered endothelial function. We tested the hypothesis that chronic endothelin receptor antagonism preserves endothelial function and increases NO in experimental porcine hypercholesterolemia. Pigs were randomized to 3 groups: Group 1, a 2% high-cholesterol (HC) diet alone (n=7); group 2, RO-48-5695, a combined endothelin receptor antagonist, and an HC diet (n=8); and group 3, ABT-627, a selective endothelin-A receptor antagonist, and an HC diet (n=8). Coronary epicardial and arteriolar endothelial function was determined by a dose-response relaxation to bradykinin (10(-11) to 10(-6) mol/L), in all groups and in pigs maintained on a normal diet. Plasma total oxidized products of NO (NO(x)) were determined by chemiluminescence at baseline and after 12 weeks. Bradykinin-stimulated coronary epicardial and arteriolar relaxation in group 1 was attenuated compared with normal-diet controls. This relaxation was normalized with endothelin receptor antagonism. Plasma NO(x) decreased after 12 weeks in group 1 (-74.8+/-5.5%). This decrease was attenuated in the endothelin receptor antagonist groups (group 2, -28.2+/-15.0%; group 3, -38.9+/-20.6%). Chronic endothelin receptor antagonism preserves coronary endothelial function and increases NO in hypercholesterolemia. This study supports a role of endothelin-1 in the regulation of NO activity and suggests a possible therapeutic role for endothelin receptor antagonists in hypercholesterolemia.

Animals↗