Enhancement Of Atherosclerosis Research Articles

Fine particulate matter air pollution and atherosclerosis: Mechanistic insights

BackgroundAtherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous plaque in the arteries. Its etiology is very complicated and its risk factors primarily include genetic defects, smoking, hyperlipidemia, hypertension, lack of exercise, and infection. Recent studies suggest that fine particulate matter (PM2.5) air pollution may also contribute to the development of atherosclerosis. Scope of reviewThe present review integrates current experimental evidence with mechanistic pathways whereby PM2.5 exposure can promote the development of atherosclerosis. Major conclusionsPM2.5-mediated enhancement of atherosclerosis is likely due to its pro-oxidant and pro-inflammatory effects, involving multiple organs, different cell types, and various molecular mediators. General significanceStudies about the effects of PM2.5inhalation on atherosclerosis may yield a better understanding of the link between air pollution and major cardiovascular diseases, and provide useful information for policy makers to determine acceptable levels of PM2.5 air quality. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.

Monocyte Angiotensin Converting Enzyme Expression May Be Associated with Atherosclerosis Rather than Arteriosclerosis in Hemodialysis Patients

Circulating monocytes can be divided into functionally distinct subpopulations according to their surface expression of CD14 and CD16. Monocytes with high-level expression of both antigens (CD14(++)CD16(+), Mo2 cells) are associated with cardiovascular morbidity and mortality in hemodialysis patients. These cells express angiotensin converting enzyme (ACE) on their surface. They are involved in the association of chronic inflammation and cardiovascular disease in kidney patients. Cardiovascular morbidity results from atherosclerosis (plaque-forming, vessel occluding disease) and arteriosclerosis (loss of arterial dampening function). It is unknown whether ACE-expressing proinflammatory monocytes are related to atherosclerosis, arteriosclerosis, or both. During baseline examination for a prospective study on monocyte ACE expression and mortality, 60 chronic hemodialysis patients of an academic outpatient center were screened for atherosclerosis by carotid artery ultrasound, for arteriosclerosis by pulse pressure measurement, and for ACE expression on Mo2 cells by flow cytometry. ACE expression on Mo2 monocytes was significantly higher in patients with severe compared with those with little or no carotid atherosclerosis. Mo2 ACE correlated with a score to semiquantify atherosclerosis and remained a significant predictor of carotid plaques in multivariate analysis including the other univariately associated variables of age, hemoglobin A1c, and albumin. Mo2 ACE was not related to pulse pressure. ACE expression on Mo2, although being a known predictor of mortality and cardiovascular disease in end-stage renal disease patients, may act via enhancement of atherosclerosis rather than arteriosclerosis.

Impaired efflux of cholesterol from aged cells and its molecular mechanism: A basis for age‐related enhancement of atherosclerosis

Aging is one of the risk factors for atherosclerotic cardiovascular diseases, however, its molecular mechanism is currently unknown. Many types of cells in the atherosclerotic lesions are considered to have various biological abnormalities such as impaired lipid homeostasis and slow cell proliferation, which may be related to senescence at cellular levels. One of the common characteristics of senescent cells in vitro is the alteration of actin cytoskeletons, which were reported to be involved in the intracellular transport of lipids. Cholesterol efflux from the cells is the initial step of reverse cholesterol transport, a major protective system against atherosclerosis. Recently, we demonstrated that Cdc42, a member of the Rho‐GTPase family, might be crucial for cellular lipid transport and cholesterol efflux based upon studies of Tangier cells that are deficient in ABCA1 gene. In the current review, we also indicate that the expression of Cdc42 is decreased in the cells from aged subjects in close association with the retarded intracellular lipid transport. Furthermore, the Cdc42 expression is reduced by culturing fibroblasts in vitro for a long duration. Werner syndrome (WS) is characterized by the early onset of senescent phenotypes including premature atherosclerotic cardiovascular diseases, although the underlying molecular mechanism for the enhanced atherosclerosis has not been fully understood yet. We examined the intracellular lipid transport and cholesterol efflux and the expression levels of cholesterol efflux‐related molecules in skin fibroblasts obtained from patients with WS. Cholesterol efflux was markedly reduced in the WS fibroblasts in association with an increased cellular cholesterol content. Fluorescent recovery after photobleaching technique revealed that intracellular lipid transport around Golgi apparatus was markedly reduced when using a C6‐NBD‐ceramide as a tracer. Cdc42 protein and its guanosine 5′‐triphosphate‐bound active form were markedly reduced in the WS fibroblasts. The adenovirus‐mediated complementation of wild‐type Cdc42 corrected the impaired cholesterol efflux, intracellular lipid transport and cellular cholesterol levels in the WS fibroblasts. These data indicate that the reduced expression of Cdc42 might be responsible for the abnormal lipid transport, which in turn might be related to the accelerated cardiovascular manifestations in WS patients. The current review focuses on the impaired efflux of cholesterol from aged cells and its molecular mechanism as a basis for age‐related enhancement of atherosclerosis.

Chlamydia pneumoniae and Cardiovascular Disease.

Chlamydia pneumoniae, a respiratory pathogen, has been suggested as a risk factor for cardiovascular disease. Epidemiologic data are very controversial. Histopathologic and microbiologic studies have established an association between atherosclerosis and presence of C. pneumoniae, consistently finding C. pneumoniae DNA and antigens in atherosclerotic arteries. C. pneumoniae has been cultured from atherosclerotic arteries in several centers. An etiologic role for C. pneumoniae in initiation, acceleration of atherosclerosis, and/or acute ischemia remains debatable. In vitro studies have shown that C. pneumoniae can induce foam cell formation, low-density lipoprotein oxidation, and proinflammatory and procoagulant cytokine expression. Animal models of de novo initiation or enhancement of atherosclerosis have been developed. Preliminary trials of secondary prevention of coronary artery disease complications by antimicrobial agents show modest results. Better diagnostic tools, more diverse animal models, and clinical trials of primary prevention are needed. Meanwhile, results of ongoing large clinical trials on secondary prevention are eagerly awaited, but may not be definitive.

Increased atherosclerosis in rabbits immunized with endothelial cells

Rabbits maintained on normal ration or cholesterol-supplemented diet were immunized with homogenates of endothelial cells grown in cultures that were derived from either bovine or human aorta. Minimal aortic lesions were found in all groups of rabbits fed regular diet; microscopically, differences were seen that manifested as medial lesions in controls and intimal lesions in animals immunized with endothelial cells. Aortic atherosclerosis was significantly increased in the immunized, cholesterol-fed animals over that in controls. This difference was more pronounced in the abdominal aorta where the area with lesions in immunized rabbits was 4–7 times that of controls; atherosclerosis of the thoracic aorta was 2.5–5 times greater in the immunized animals ( P < 0.001 for both segments). Increased atherosclerosis was observed despite a significant reduction in plasma cholesterol in the immunized rabbits (770 ± 119 mg/dl) compared to controls (1595 ± 225 mg/dl) ( P < 0.001). Immunization with endothelial cells elicited strong cell-mediated and humoral responses as determined by dermal delayed hypersensitivity and solid-phase immunoradiometric tests, respectively. Cross-reactivity in both assays was found against human and bovine cells. Enhancement of atherosclerosis appears to depend not on induction of immune complexes but on specific antibodies and cell-mediated reactions.

Release of Plasminogen Activator from Isolated Perfused Dog Heart

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.

The effectiveness of chemical carcinogens to induce atherosclerosis in the white Carneau pigeon

The frequency of atherosclerotic lesions of the abdominal aorta has been reported to increase significantly in chickens exposed to benzo[ a]-pyrene and 7,12-dimethylbenz[ a, h]anthracene. The present studies were performed to determine in another experimental model frequently used in atherosclerotic studies (i.e. White Carneau Pigeons) whether these and other chemical carcinogens enhnance atherosclerosis. The induction and enhancement of atherosclerotic lesions were observed in pigeons treated with 7,12-dimethylbenz[ a, h]anthracene, benzo[ a]pyrene and 3-methylcholanthrene. The number and size of plaques in the aorta were frequently greater in pigeons treated with the higher concentration (i.e. 100 mg/kg) of these 3 polycyclic aromatic hydrocarbons. Benzo[ e]pyrene and 2,4,6,-trichlorophenol were ineffective in the induction or enhancement of atherosclerosis in the pigeons. The results of the present and previous studies suggest that the polycyclic aromatic hydrocarbons (excluding benzo[ e]pyrene) may be the only potential atherogens in avian atherosclerosis. This relationship may be associated with how these hydrocarbons are transported in the plasma (i.e. by lipoproteins) as demonstrated by the present distribution studies.

Carbon monoxide, tobacco smoking, and the pathogenesis of atherosclerosis 1

Carbon monoxide (CO) exposure, which results in mean carboxyhemoglobin levels of 10%, enhances the incidence of coronary artery atherosclerosis in female White Carneau pigeons which have been made hypercholesterolemic by addition of cholesterol to their diet. CO is, however, without effect on normocholesterolemic birds. Aortic cholesterol levels are increased by CO exposure but phospholipid and triglyceride levels are reduced in hypercholesterolemic birds. These effects might be due to inhibition of lysosomal enzyme activity. The level of CO exposure, the duration of that exposure, and the level of dietary cholesterol are critically interdependent factors which can influence the extent of CO involvement in the pathogenesis of the disease. CO enhancement of atherosclerosis seems to be significant in the pigeon, during early lesion development when arterial lipid accumulation may be greatest.