SEARCH · PubMed Health

Results for “Hypercholesterolemia”

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 55 records · Page 3Linked to original sources

PubMed1994

Dietitian practices for adult outpatients with hypercholesterolemia referred by physicians. The Minnesota Dietitian Survey.

OBJECTIVE: To characterize the physician-to-dietitian referral process and dietitian practice patterns and opinions related to adult outpatients with hypercholesterolemia. DESIGN: Cross-sectional mail survey. PARTICIPANTS: Minnesota dietitians who treat adult outpatients referred by physicians for hypercholesterolemia. MAIN OUTCOME MEASURES: Proportion of patients for whom background information or specific diet instructions were provided by referring physicians and for whom follow-up was recommended and dietary fat content calculated by the dietitians. RESULTS: Completed questionnaires were returned by 216 of 267 eligible dietitians (81% response rate). Respondents saw, on average, 31 referred patients per month, 31% of whom were referred for hypercholesterolemia, 31% for type II diabetes mellitus, and 24% for obesity. For patients referred for hypercholesterolemia, background information was provided by physicians 37% of the time, and specific diet instructions 15% of the time. One or more follow-up visits by the dietitians were recommended for 42% of patients referred for hypercholesterolemia, compared with 60% and 70% of patients referred for diabetes and obesity, respectively. The average number of additional visits within 6 months of the initial consultation recommended by dietitians was 2.0 for patients referred for hypercholesterolemia, 3.5 for patients referred for diabetes, and 6.7 for patients referred for obesity, and the number of visits that occurred was half or less than that recommended. Dietary fat content was calculated by the dietitians for only 25% of patients referred for hypercholesterolemia. CONCLUSIONS: For adult outpatients referred to dietitians for hypercholesterolemia, relevant patient information is usually not provided by referring physicians, the number of follow-up visits is well below what would reasonably be expected to produce significant and sustained eating behavior change, and calculation of dietary fat content is generally not done. More research is needed to determine appropriate nutrition intervention protocols for these patients.

Adult↗

PubMed1994

Systemic hypertension and hypercholesterolemia in vein grafts: effects on the function and morphology of experimental vein grafts.

Hypertension and hypercholesterolemia are known risk factors for the development of atherosclerosis and are considered to influence the development of vein graft intimal hyperplasia. This study examines the effect of hypertension (two-kidney, one-clip model for 8 weeks) and hypercholesterolemia (1% cholesterol diet for 8 weeks) individually and in combination on the formation of intimal hyperplasia and the vasomotor function of vein grafts. Forty New Zealand White rabbits underwent a carotid vein bypass graft. Ten were controls, 10 were hypertensive, 10 were hypercholesterolemic, and 10 had both hypertension and hypercholesterolemia. Hypertension and/or hypercholesterolemia were present for 4 weeks prior to and for 4 weeks after surgery. All vein grafts were harvested at 4 weeks postoperatively for histology (n = 6) or contractility studies (n = 4). Compared to controls, hypercholesterolemia increased intimal but not medial thicknesses of the vein grafts and enhanced smooth muscle cell contractility. Hypertension did not increase vein graft intimal or medial thicknesses but did augment vein graft contractility compared to controls. Hypertension with hypercholesterolemia increased intimal and medial thicknesses and enhanced vasoreactivity in vein grafts. The results show that hypertension influences the vasoreactivity but not the development of intimal hyperplasia in vein grafts. When hypertension is combined with hypercholesterolemia, there is both an increase in the medial thickness and an attenuation of vasomotor function compared to hypercholesterolemia alone, although there is no further increase in intimal hyperplasia formation. Therefore, this study suggests that the combination of both atherogenic risk factors does not act synergistically in promoting either the formation of intimal hyperplasia or vasomotor dysfunction in vein grafts.

Animals↗

PubMed2006

Recovery from vecuronium is delayed in patients with hypercholesterolemia.

PURPOSE: To examine the effects of hypercholesterolemia with respect to onset time and recovery from vecuronium-induced neuromuscular block. METHODS: A randomized controlled trial was undertaken in 20 adult patients with hypercholesterolemia (hypercholesterolemia group) and 20 healthy patients with normal serum cholesterolemia (control group). Following induction of anesthesia, vecuronium 0.1 mg.kg(-1) iv was administered. Onset of neuromuscular block and recovery times in the two groups were compared using supramaximal stimulation of the ulnar nerve. RESULTS: The supramaximal stimulating current in the hypercholesterolemia group was similar to that of the control group (38.1 +/- 15.5 vs 31.3 +/- 7.6 mA, P = 0.087). Onset of vecuronium-induced neuromuscular block (time to loss of response to T1) in the hypercholesterolemia group was similar to that observed in the control group (243 +/- 84 vs 249 +/- 56 sec, P = 0.792). Times from vecuronium administration to the return of T1 were also similar in the two groups (29.8 +/- 9.7 vs 25.3 +/- 6.8 min, P = 0.099). However, mean times for return of T2, T3, and T4 in the hypercholesterolemia group were longer than in the control group (44.5 +/- 14.4 vs 34.0 +/- 8.4 min for T2, P = 0.018). During recovery from neuromuscular block, T1/control and train-of-four ratio in the hypercholesterolemia group were less than in the control group, 90-120 min and 70-120 min after vecuronium, respectively (P < 0.05). CONCLUSION: Recovery from vecuronium-induced neuromuscular block is delayed in patients with hypercholesterolemia.

Aged↗

PubMed1997

Platelet alpha 2-adrenergic receptors in hypercholesterolemia: relationship between binding studies and epinephrine-induced platelet aggregation.

BACKGROUND: Platelets isolated from patients with hypercholesterolemia are more sensitive in vitro to various aggregating agents, including epinephrine, than those isolated from normocholesterolemic subjects. Increased platelet reactivity is one mechanism that may explain the enhanced risk of thromboembolism in hypercholesterolemia. This study assessed whether platelet hyperreactivity to epinephrine in hypercholesterolemia is associated with higher alpha 2-adrenergic receptor density or affinity for epinephrine. METHODS: Platelet aggregation and binding studies, with use of [3H]yohimbine as ligand, were performed on platelets isolated from 30 patients with type IIa hypercholesterolemia and 23 control subjects. RESULTS: Platelet aggregation in response to epinephrine was significantly higher in patients with hypercholesterolemia than in control subjects. A statistically significantly higher alpha 2-adrenergic receptor density was observed in a subgroup of 13 patients with hypercholesterolemia than in 13 sex- and age-matched control subjects (280 +/- 61 and 230 +/- 49 fmol/mg protein respectively; p < 0.03), but no difference was observed in receptor affinity for the ligand. In these subgroups plasma total and levels of low-density lipoprotein (LDL) cholesterol were inversely correlated with platelet aggregation but directly correlated with platelet receptor density. CONCLUSION: Platelet alpha 2-adrenergic receptor density is increased in hypercholesterolemia and directly correlates with plasma total and levels of LDL cholesterol, providing at least a partial explanation for the enhanced platelet response to epinephrine that is observed in hypercholesterolemia.

Adrenergic alpha-Antagonists↗

PubMed2005

Has control of hypercholesterolemia and hypertension in type 1 diabetes improved over time?

OBJECTIVE: To determine the extent to which patients' awareness, treatment, and control of hypertension and hypercholesterolemia have changed over time and to examine factors associated with awareness and treatment in a type 1 diabetes population. RESEARCH DESIGN AND METHODS: Data from six examinations conducted over 10 years from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective study of subjects with childhood-onset (<17 years of age) type 1 diabetes diagnosed between 1950 and 1980 and followed since 1986, were analyzed. Hypertension and hypercholesterolemia were defined according to the concurrent Joint National Committee and National Cholesterol Education Program Adult Treatment Panel criteria, respectively. RESULTS: Results demonstrated that awareness of both conditions has improved; however, control is not optimal (e.g., only 32.1 and 28% of those with hypertension in 1986-1988 and 1996-1998 were controlled, while for hypercholesterolemia, the rates were 0 and 5.5%, respectively). Stratified by age-group (18-29, 30-39, and >40 years), the youngest subjects with hypercholesterolemia were least likely to be treated and controlled to goal levels. Older age and physician contact were correlates of awareness and treatment of hypertension at baseline, while presence of renal or coronary complications was also associated with awareness and treatment of both hypertension and hypercholesterolemia at the 10-year follow-up. CONCLUSIONS: There is a considerable treatment gap, particularly for hypercholesterolemia. Improved treatment of both hypertension and hypercholesterolemia are clearly needed, particularly hypercholesterolemia in younger age-groups who have not yet experienced long-term complications.

Adult↗

PubMed1999

Natural history of hypercholesterolemia in systemic lupus erythematosus.

OBJECTIVE: To determine the natural history of hypercholesterolemia in the first 3 years of disease in an inception cohort of patients with systemic lupus erythematosus (SLE) followed at a single center and to determine the influence of hypercholesterolemia on the subsequent development of coronary artery disease (CAD) related events. METHODS: We identified patients who were seen at the University of Toronto lupus clinic within 1 year of diagnosis from January 1, 1974, to December 31, 1987, and who were seen at least once a year in the first 3 years. Patients were divided into 3 groups: Normal cholesterol: serum total cholesterol (TC) < 5.2 mmol/l throughout the 3 year period of study. Sustained hypercholesterolemia: at least one measurement of TC of > 5.2 mmol/l in each of the first 3 years at the clinic. Variable hypercholesterolemia: TC > 5.2 mmol/l in no more than 2 of the first 3 years of followup. Patients were followed from inception until the present day. The primary outcome was the time of the first CAD related event (myocardial infarction, angina, or sudden unexplained death). RESULTS: One hundred thirty-four patients (118 women, 16 men) were studied: 33 (24.6%) had normal cholesterol, 54 (40.3%) had sustained hypercholesterolemia, and 47 (35.1%) had variable hypercholesterolemia. Using multiple logistic regression the best predictors of sustained hypercholesterolemia were cumulative dose of steroids, no antimalarial therapy, and age of onset of SLE > 35 years old. CAD related events occurred in 1 (3%) of the normal TC group, 3 (6.4%) of the variable group, and in 15 (27.8%) of the sustained group (p = 0.003), 79% of all CAD events occurred in the sustained group. The best predictors of CAD were sustained hypercholesterolemia, lung involvement, and age at onset of SLE > 35 years. CONCLUSION: Within 3 years of diagnosis, 75.4% of patients with SLE had elevated TC, which was sustained in 40.3% of all patients. Older age at onset as well as increased cumulative dose of steroids and no antimalarial therapy are significant predictors of this group. It is this group that experiences the majority of CAD related events. Aggressive lipid lowering therapy should be targeted at such patients.

Age of Onset↗

PubMed2005

Colorectal cancer and hypercholesterolemia: review of current research.

AIM: In spite of ample research about a high level of cholesterol in the blood of patients with colorectal cancer (CRC), the relationship between factors causing hypercholesterolemia and factors leading to CRC development is not fully investigated. The purpose of this article is to provide a review of the current research about the risk factors leading to the development of hypercholesterolemia and CRC, and to show the relationship between these factors, hypercholesterolemia and CRC with the implication for CRC preventive and treatment practices. METHODS: A systematic search of MEDLINE and PUBMED databases between 1990 and 2005 was conducted to locate the studies that investigated the risk factors causing CRC and hypercholesterolemia. From among 255 studies found, 66 were selected that matched the following criteria for selection: (1) reported original research; (2) discussed at least one of the listed eight factors; (3) discussed hypercholesterolemia; and/or (4) discussed colon or rectum cancer. RESULTS: The studies were grouped according to four areas of research: (1) studies that explored the relationship between different factors and CRC incidences; (2) studies that investigated the relationship between different factors and CRC incidences and the role of mutations in causing CRC; (3) studies that looked at the factors causing hypercholesterolemia; and (4) studies that explored the relationship among the factors, hypercholesterolemia, and CRC development. A discussion of the studies is presented and the details related to the studies major aspects are summarized in 4 tables. CONCLUSION: The review has revealed a relationship between factors that can lead to the development of CRC and those that lead to hypercholesterolemia. Although the role of many individual risk factors is still controversial the analysis of their significance in combination might be important for diagnostic and development of the models for prediction of cancer occurrence.

Colorectal Neoplasms↗

PubMed1991

Family history fails to identify many children with severe hypercholesterolemia.

Optimal strategies for identifying children with hypercholesterolemia have not been established. Several groups have advocated that testing of serum cholesterol levels be limited to those children who have family histories of hyperlipidemia or premature coronary heart disease. We studied the ability of comprehensive family histories to identify children with hyperlipidemia in a group of 114 children (mean age, 8 +/- 4 years) who were referred for treatment of hypercholesterolemia. A positive family history was defined according to guidelines of the American Academy of Pediatrics. The mean fasting total cholesterol in the children was 5.74 +/- 1.42 mmol/L (222 mg/dL). Family history was negative for hypercholesterolemia or premature coronary heart disease in 22 (22%) of 100 children with total cholesterol levels greater than the 75th percentile for their ages, in 13 (18.3%) of 71 children with total cholesterol levels greater than the 95th percentile for their ages, and in four (11.8%) of 34 children with presumed heterozygous familial hypercholesterolemia. Of the 78 children who had both hypercholesterolemia and positive family histories, hyperlipidemia was reported in 72 families, whereas premature heart disease was reported in only 27. We conclude that in a population of children referred because of known hypercholesterolemia, a detailed family history not only fails to identify many children with mild hypercholesterolemia, but also fails to identify a significant proportion of children with markedly elevated cholesterol levels. Additionally, in families of children with hypercholesterolemia, a history of hyperlipidemia is more common than a history of premature heart disease.

Adolescent↗

PubMed1997

Trends in cholesterol knowledge and screening and hypercholesterolemia awareness and treatment, 1980-1992. The Minnesota Heart Survey.

BACKGROUND: National cholesterol education initiatives were implemented in the middle to late 1980s. This study examines whether there were significant increases in population cholesterol knowledge and screening and hypercholesterolemia awareness and treatment from 1980 to 1992. METHODS: Three population-based surveys were conducted among adults aged 25 to 74 years in 1980-1982 (N = 4086), 1985-1987 (N = 5735) and 1990-1992 (N = 6305) in the Minneapolis-St Paul, Minn, metropolitan area as part of the Minnesota Heart Survey. Personal interviews about knowledge of cholesterol level and hypercholesterolemia awareness and treatment were conducted. Total serum cholesterol was measured; hypercholesterolemia was defined as having a total cholesterol level of 6.21 mmol/L or more (> or = 240 mg/dL) or current use of cholesterol-lowering medications. Hypercholesterolemia awareness was defined as the belief of a participant with hypercholesterolemia that her or his total cholesterol was high. RESULTS: Knowledge increased from 15% in 1980-1982 to 17% in 1985-1987 to 55% in 1990-1992 (P < .001) in women; similar trends were observed for men (19%, 22%, and 47%, respectively; P < .001). Hypercholesterolemia awareness doubled during the decade (women: 17%, 1980-1982; 24%, 1985-1987; 60%, 1990-1992; P < .001; men: 25%, 30%, and 55%, respectively; P < .001). Among participants who reported physician-diagnosed hypercholesterolemia, the prevalence of current pharmacological treatment increased from 9% in 1980-1982 to 14% in 1990-1992 in women, and from 7% to 13%, respectively, in men. CONCLUSIONS: Cholesterol knowledge and hypercholesterolemia awareness and treatment increased substantially during the 1980s, concurrent with educational initiatives of the National Cholesterol Education Program and other efforts.

Adult↗

PubMed1991

[Diagnostic and functional significance of arcus lipoides in hypercholesterolemia].

Twenty-eight patients were studied who required treatment for hypercholesterolemia type IIa. Familial hypercholesterolemia was found in 53%. Sixty percent of all patients had arcus senilis. When familial and non-familial hypercholesterolemia were compared the incidence of arcus senilis was 80% and 38%, respectively. The gradation of the condition was minor (n = 9), moderate (n = 4), or pronounced (n = 4); all patients with a strong degree and 7 of 8 patients with either moderate or pronounced arcus senilis had familial hypercholesterolemia. The mean cholesterol level was 345 +/- 82 in patients with familial hypercholesterolemia and 353 +/- 120 mg/dl in patients with non-familial hypercholesterolemia. Although the correlation between the cholesterol level and the degree of arcus senilis was higher in patients with familial hypercholesterolemia than in those with non-familial hypercholesterolemia (r = 0.45 versus r = 0.17), neither had clinical relevance. There was no connection between the cholesterol level, refraction or visual acuity. The mean contrast sensitivity measured for five different spatial frequencies in all patients was normal. In comparison with patients without arcus senilis, the mean values in patients with severe arcus senilis showed lower contrast sensitivity for the higher spatial frequencies.

Adult↗

PubMed2003

Use of nutritional supplements for the prevention and treatment of hypercholesterolemia.

OBJECTIVE: Hypercholesterolemia is a major risk factor for the development of coronary artery disease. Studies have shown that several vitamins and nutritional supplements may contribute to a reduction in total and low-density lipoprotein cholesterol. This goal of this study was to document the use of vitamins and nutritional supplements that may treat or prevent hypercholesterolemia. METHODS: Secondary analysis of the National Health and Nutrition Examination Survey III responses from 13,990 patients were available to use for making population estimates. RESULTS: Of those individuals with a known diagnosis of hypercholesterolemia, 3.6% were taking at least one vitamin or nutritional supplement to decrease cholesterol levels. For individuals trying to prevent hypercholesterolemia, 1.2% were using one of these vitamin or nutritional supplements. Only 0.7% of individuals without or trying to prevent hypercholesterolemia used one of these specific supplements. We used multivariate analysis to control for several factors, and individuals with a diagnosis of hypercholesterolemia had an adjusted odds ratio of 2.10 (95% confidence interval, 1.38-3.21) for vitamin use compared with those without or trying to prevent high cholesterol. Those trying to prevent hypercholesterolemia had an adjusted odds ratio of 0.69 (95% confidence interval, 0.48-1.00) for vitamin use compared with those without or trying to prevent high cholesterol. CONCLUSIONS: The use of vitamins and nutritional supplements that may reduce total and low-density lipoprotein cholesterol levels is low in the United States. Future research is needed to confirm the effectiveness of these products, examine the quality and purity of currently available products, and explore whether using these supplements are an adequate low-cost alternative to pharmaceuticals now available.

Adolescent↗

PubMed1992

Interactions of hypercholesterolemia and hypertension in initiation of glomerular injury.

In the Dahl S rat (DS), salt induces systemic and glomerular capillary hypertension associated with progressive glomerulosclerosis, while Dahl R rats (DR) remain normotensive, without glomerular abnormalities. Studies in experimental models have suggested that hypercholesterolemia may play a role in the development of glomerulosclerosis; however, it is unclear whether hypercholesterolemia alone, in the absence of hypertension, can initiate injury. To answer this question we induced hypercholesterolemia in salt-supplemented DS (DSC) and DR (DRC) by feeding a high cholesterol (4%) chow. Control rats (DS, DR) received high-salt, normal cholesterol chow. After eight weeks, DS and DSC developed equivalent hypertension (161 +/- 3 vs. 153 +/- 3 mm Hg, respectively, P = NS), while DR and DRC remained normotensive (138 +/- 5 vs. 131 +/- 5 mm Hg, P = NS; P less than 0.05 vs. DS and DSC). Cholesterol fed rats developed marked and equivalent hypercholesterolemia compared to controls (DS vs. DSC, 71 +/- 3 vs. 289 +/- 91 mg/dl, P less than 0.05; DR vs. DRC, 52 +/- 2 vs. 327 +/- 54 mg/dl, P less than 0.05). Hypertensive rats (DS, DSC) developed worse proteinuria and glomerular injury than normotensive rats (DR, DRC), but hypercholesterolemia exacerbated proteinuria and glomerulosclerosis only in DSC and not in DRC. Proteinuria significantly correlated with serum cholesterol in hypertensive rats (DS, DSC, P less than 0.05), but not normotensive rats (DR, DRC, P = NS). Furthermore, DSC had increased renal vascular resistance compared to DS, while no differences were found between DRC and DR. Thus, in the Dahl rat, hypercholesterolemia alone does not initiate glomerular injury. In this model, hypercholesterolemia is a pathogenetic factor in glomerular injury only when it coexists with systemic hypertension.

Animals↗

PubMed2000

Hypercholesterolemia is associated with increased kidney graft loss caused by chronic rejection in male patients with previous acute rejection.

BACKGROUND: Whereas acute rejection is the main risk factor for the occurrence of chronic rejection, mechanisms in addition to the donor-specific immune response probably contribute to late allograft failure. In this study, we investigated the possible role of hypercholesterolemia in the incidence of chronic kidney graft loss. METHODS: By using the actuarial method, we retrospectively analyzed the long-term loss of cadaveric kidney grafts in patients who had a functioning graft at 1 year and had received a transplant and undergone cyclosporin A therapy in our center between 1983 and 1997. RESULTS: As observed previously, patients with acute rejection during the 1st posttransplant year (n=198) had significantly higher actuarial graft loss at 10 years compared with those free of acute rejection (n=244). In patients free of acute rejection at 1 year, hypercholesterolemia (> or =250 mg/dl) had no impact on graft loss at 10 years. On the contrary, in patients with previous acute rejection, those with hypercholesterolemia (n=59) had a higher immunological (36.0% vs. 19.2%; P<0.01) and overall (50.0% vs. 25.3%; P<0.01) graft loss at 10 years compared with patients with serum cholesterol <250 mg/dl (n=139). Among patients with 1st year acute rejection, hypercholesterolemia was associated with a significant increase in graft loss in male but not in female recipients. Multivariate analysis confirmed that hypercholesterolemia was an independent risk factor for chronic graft loss in male patients (P<0.05). CONCLUSION: Hypercholesterolemia is an independent risk factor for kidney graft loss from chronic rejection in male patients with previous acute rejection. Correction of hypercholesterolemia could help to reduce kidney graft loss caused by chronic rejection in this category of patients.

Acute Disease↗

PubMedDate not supplied

Connexin43 gene expression in the rabbit arterial wall: effects of hypercholesterolemia, balloon injury and their combination.

The specialized functions of endothelium require intercellular communication between endothelial cells within the monolayer, and between endothelium and other cells present in the vessel wall. This is accomplished by a combination of paracrine soluble mediators and direct gap-junctional intercellular communication (GJIC) mediated by a family of connexin proteins. A prominent connexin expressed by vascular cells in vivo and in vitro is connexin 43 (Cx43). We have investigated the in vivo gene regulation of Cx43 in the context of vascular pathology, as a result of mechanical injury, hypercholesterolemia or both. The aortoiliac bifurcation in the rabbit was examined following three types of insult: (1) diet-induced hypercholesterolemia resulting in macrophage-rich fatty streak lesions, (2) mechanical, stretch-denudation injury resulting in intimal smooth muscle cell (SMC) proliferation and (3) mechanical injury superimposed on hypercholesterolemia resulting in a complex vascular lesion having characteristics of both interventions. The normal rabbit iliac artery expressed approximately equal levels of Cx43 mRNA in the medial SMC layers and in the endothelium. In hypercholesterolemia-induced atherosclerosis, Cx43 expression was most prominent in macrophage foam cells even though normocholesterolemic precursor monocytes did not express Cx43 mRNA. Antibodies directed specifically to Cx43 protein confirmed the expression of macrophage gap junction protein in these cells. Medial SMC in hypercholesterolemia exhibited less Cx43 than their normal counterparts in control animals. Mechanical injury in the absence of hypercholesterolemia resulted in intimal thickening in which Cx43 expression in the intimal SMC was equivalent to that in the subjacent medial SMC, both being approximately equivalent to normal uninjured rabbit medial SMC expression. Cell-specific expression of Cx43 in combined mechanical injury/hypercholesterolemia was similar to that observed in hypercholesterolemia alone: Cx43 upregulation in macrophages, while medial SMC were downregulated. Normo- and hypercholesterolemic alveolar macrophages of the lung and Kupffer cells of the liver did not exhibit induction of Cx43 mRNA, nor did macrophages isolated from peritoneal or bronchial lavage fluid of the same animals. This work extends our previous finding of Cx43 upregulation in human atherectomy tissue and demonstrates that atherosclerotic lesions in situ, in a controlled animal model of atherosclerosis, exhibit cell-specific changes in Cx43 gene expression. Changes in medial SMC migration, proliferation and phenotype, as well as enhanced interactions between adherent/infiltrating monocytes and endothelium may be related to modified GJIC pathways in the vessel wall.

Animals↗

PubMed2004

Hypercholesterolemia impairs transduction of vasodilator signals derived from ischemic myocardium: myocardium-microvessel cross-talk.

OBJECTIVE: Coronary microvessels are functionally coupled to the myocardial metabolic state. In hypercholesterolemia, the coronary vascular dysfunction extends to microvascular levels. We hypothesized that the vasodilator signal transduction from ischemic heart is impaired in the coronary microvascular wall of hypercholesterolemia. METHODS AND RESULTS: Rabbits were fed with normal chow (control group) or 2% high-cholesterol diet (hypercholesterolemia group) for 8 weeks. Coronary microvessels isolated from rabbit hearts were pressurized and gently placed on a beating canine heart. Myocardial ischemia was produced in the beating heart and the diameter of the isolated microvessel was observed using an intravital microscope with a floating objective. In control group, the isolated microvessels significantly dilated 2 minutes after the onset of ischemia, and a plateau was observed at 10 minutes. In contrast, the microvessels from hypercholesterolemia group did not dilate during ischemia. Dihydroethidium fluorescence microscopy revealed an elevated superoxide level in the microvessels of hypercholesterolemia group. The application of tiron (free radical scavenger) significantly dilated the isolated microvessels only from hypercholesterolemic animals. CONCLUSIONS: We conclude that the transduction of vasodilator signals derived from ischemic myocardium is impaired in the coronary microvascular wall of hypercholesterolemia. Enhanced oxidative stress in hypercholesterolemia may alter the microvascular function.

Acetylcholine↗

PubMed1985

Effects of noise exposure and hypercholesterolemia on auditory function in the New Zealand white rabbit.

An association between hypercholesterolemia and high-frequency hearing loss has been suggested previously. Most data have been epidemiologic, and only recently have experimental studies appeared supporting this observed association. It is unclear whether this hearing loss is related solely to hypercholesterolemia or if it is a consequence of cholesterol-induced vascular changes. The New Zealand White rabbit was used to study the auditory effects of noise, hypercholesterolemia, and the combination of both. Auditory function was evaluated with far-field monitoring of click-evoked auditory brain stem responses by comparing latency/intensity functions and absolute click-evoked thresholds. Hypercholesterolemia was maintained for only 3 weeks, theoretically eliminating atherosclerotic vascular changes as a mechanism contributing to observed changes. Auditory function was unchanged after 3 weeks of hypercholesterolemia. Also, the changes observed after noise exposure were comparable between the normal and the hypercholesterolemic groups. We conclude that if hypercholesterolemia contributes to high-frequency hearing loss, the pathophysiology is related to cholesterol-induced vascular changes, not solely to hypercholesterolemia.

Animals↗

PubMed2004

Hypercholesterolemia impairs angiogenesis in patients with breast carcinoma and, therefore, lowers the risk of metastases.

Our aim was to study the effect of hypercholesterolemia on angiogenesis induced by breast carcinoma. Of 51 patients with invasive ductal carcinoma, 28 had hypercholesterolemia and 23 had normocholesterolemia. The intratumoral microvessel density (MVD) was evaluated by using anti-CD31 antibody. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on endothelial and tumor cells was examined and graded semiquantitatively. Patients with normocholesterolemia had a higher MVD (76.4 +/- 8.2) than those with hypercholesterolemia (54.6 +/- 5.1) (P < .01). The risks of recurrence and distant metastasis were higher in patients with normocholesterolemia than in patients with hypercholesterolemia (P < .01). Patients with hypercholesterolemia showed lower expression of endothelial VEGF and bFGF than patients with normocholesterolemia (P < .05 and P < .01, respectively). In addition, tumoral bFGF and VEGF expression showed negative correlation with the presence of hypercholesterolemia (P < .01). We suggest that hypercholesterolemia impairs angiogenesis by suppressing endothelial and tumoral bFGF and VEGF expression and, therefore, lowers the risk of metastases in cases of invasive breast carcinoma.

Angiogenesis Inhibitors↗

PubMed2001

Hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic T cell responses.

The immune system has to be optimally balanced to be highly effective against infections with cytopathic microbial pathogens and must guarantee efficient destruction of cells infected with noncytopathic agents while leaving the integrity of noninfected cells largely unaltered. We describe here the effects of genetically induced hypercholesterolemia on cellular immunity in apolipoprotein E (ApoE(-/-)) and low density lipoprotein receptor-deficient (LDLR(-/-)) mice during infection with the hepatotropic lymphocytic choriomeningitis virus WE strain. In both ApoE(-/-) and LDLR(-/-) mice hypercholesterolemia aggravated virus-induced immunopathologic liver disease. ApoE(-/-) mice exhibited a higher susceptibility to virus-induced immunopathology than LDLR(-/-) mice and usually succumbed to immunopathologic disease when infected with high doses of virus. Initial virus spread was not influenced by the hypercholesterolemia, whereas clearance of the virus from spleen and nonlymphoid organs, including liver, was delayed. Activation of antiviral CTL, measured by ex vivo cytotoxicity and IFN-gamma production, and recruitment of specific CTL into blood and liver were impaired in hypercholesterolemic mice, indicating that hypercholesterolemia had a significant suppressive effect on cellular immunity. Taken together, these data provide evidence that hypercholesterolemia suppresses antiviral immune responses, thereby changing the host-virus balance, and can increase susceptibility to acute or chronic and potentially lethal virus-induced immunopathologic disease. These findings impinge on our understanding of hypercholesterolemia as a disease parameter and may explain aspects of the frequent association of persistent pathogens with hypercholesterolemia-induced diseases, such as atherosclerosis.

Animals↗