Showing papers on "Fatty streak published in 2000"

Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice

Abstract: Background—Atherosclerosis is associated with immune responses to oxidized lipoproteins and certain microorganisms, but the role of specific immunity has remained unclear. Methods and Results—To study the role of immunity in atherosclerosis, we crossed atherosclerosis-prone apoE—/– mice with immunodeficient scid/scid mice. The offspring showed a 73% reduction in aortic fatty streak lesions when compared with immunocompetent apoE–/– mice. Transfer of CD4+ T cells from apoE–/– to immunodeficient apoE–/–/scid/scid mice increased lesions by 164%. This was associated with the infiltration of transferred T cells into lesions, increased circulating interferon-γ levels, and increased I-A expression in lesions. Conclusions—CD4+ T cells carry disease-promoting immunity in atherosclerosis.

Associations of Coronary Heart Disease Risk Factors With the Intermediate Lesion of Atherosclerosis in Youth

Abstract: The raised fatty streak (fatty plaque) is the gross term for the lesion intermediate between the juvenile (flat) fatty streak and the raised lesion of atherosclerosis. We measured the percentage of intimal surface involved with flat fatty streaks, raised fatty streaks, and raised lesions in the aortas and right coronary arteries of 2876 autopsied persons aged 15 through 34 years who died of external causes. Raised fatty streaks were present in the abdominal aortas of approximately 20% of 15- to 19-year-old subjects, and this percentage increased to approximately 40% for 30- to 34-year-old subjects. Raised fatty streaks were present in the right coronary arteries of approximately 10% of 15- to 19-year-old subjects, and this percentage increased to approximately 30% for 30- to 34-year-old subjects. The percent intimal surface involved with raised fatty streaks increased with age in both arteries and was associated with high non-high density lipoprotein (HDL) and low HDL cholesterol concentrations in the abdominal aorta and right coronary artery, with hypertension in the abdominal aorta, with obesity in the right coronary artery of men, and with impaired glucose tolerance in the right coronary artery. Associations of risk factors with raised fatty streaks became evident in subjects in their late teens, whereas associations of risk factors with raised lesions became evident in subjects aged >25 years. These results are consistent with the putative transitional role of raised fatty streaks and show that coronary heart disease risk factors accelerate atherogenesis in the second decade of life. Thus, long-range prevention of atherosclerosis should begin in childhood or adolescence.

Inhibition of Early Atherogenesis by Losartan in Monkeys With Diet-Induced Hypercholesterolemia

Abstract: Background—Angiotensin II may contribute to atherogenesis by facilitating the proliferative and inflammatory response to hypercholesterolemia. This study determined, in a primate model of diet-induced atherosclerosis, the effect of AT1 blockade on fatty-streak formation, plasma lipids, and surrogate markers of vascular injury. Methods and Results—Male cynomolgus monkeys fed a diet containing 0.067 mg cholesterol/kJ for 20 weeks were given losartan (180 mg/d, n=6) or vehicle (n=8) for 6 weeks starting at week 12 of the dietary regimen. Arterial pressure, heart rate, plasma total and lipoprotein cholesterol concentrations, and lipoprotein particle sizes and subclass distributions were unaffected by treatment. Losartan caused significant (P<0.05) increases in plasma angiotensin II and angiotensin-(1–7). Compared with vehicle-treated controls, losartan reduced the extent of fatty streak in the aorta, the coronary arteries, and the carotid arteries by ≈50% (P<0.05). A significant (P<0.05) reduction in the susc...

Prominent Role of P-Selectin in the Development of Advanced Atherosclerosis in ApoE-Deficient Mice

Abstract: Background—Adhesive interactions between leukocytes and endothelial cells are characteristic of the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor–deficient mice on an atherogenic diet. The main purpose of this study is to examine the role of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. Methods and Results—We intercrossed P-selectin–deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE−/− P+/+) and without P-selectin (apoE−/− P−/−) that were fed normal mouse chow. At 4 months of age, apoE−/− P−/− mice had 3.5-fold smaller aortic sinus lesions than apoE−/− P+/+ mice. These were limited to fatty streaks in the apoE−/− P−/− mice, whereas 70% of apoE−/− P+/+ lesions contained smooth muscle cells. Signif...

Atherosclerosis: the emerging role of inflammation and the CD40-CD40 ligand system.

Abstract: Atherosclerosis is a principal cause of death in the Westernized world. Previously, it was thought to be a disease primarily involving lipid accumulation in the arterial walls. The inflammatory cells found at the sites of fatty streaks as well as in the more advanced lesions were not considered to be principally responsible for the disease. A different view of atherosclerosis has emerged subsequently. Current concepts of this disease include involvement of the immune system and chronic inflammation as crucial elements in the initiation of endothelial cell dysfunction, in fatty streak formation, and in development of advanced lesions and eventual vessel rupture (for a recent review, see ref. 1). Atherosclerosis can now be viewed as a problem of wound healing and of chronic inflammation. Numerous reports in the past few years have demonstrated clearly that migratory immune cells, including monocytes and T lymphocytes, are key cellular elements at all stages of atherosclerosis. Most exciting and relevant to atherosclerosis as a disease of chronic inflammation are papers by Schonbeck et al. (2) and Lutgens et al. (3) appearing in this issue of PNAS. These research groups clearly show that disruption of the CD40–CD40 ligand (L) system, a key mediator of cell communication in the immune system, prevents progression of established atherosclerotic lesions to more advanced unstable lesions. This evidence, coupled with recent studies showing that disruption of the CD40–CD40L system can retard the initiation of arterial plaque formation, provides compelling evidence for the role of chronic inflammation and elements of the immune response in atherosclerosis. Moreover, these investigations identify CD40–CD40L as key regulators of this process and recognize them as potentially important therapeutic targets.

Maternal Hypercholesterolemia Enhances Atherogenesis in Normocholesterolemic Rabbits, Which Is Inhibited by Antioxidant or Lipid-Lowering Intervention During Pregnancy An Experimental Model of Atherogenic Mechanisms in Human Fetuses

Abstract: Maternal hypercholesterolemia during pregnancy is associated with a marked increase in aortic fatty streak formation in human fetuses and faster progression of atherosclerosis during normocholesterolemic childhood. However, the mechanisms responsible are unknown, and the contribution of genetic differences is difficult to assess in humans. The goal of this study was to determine whether maternal hypercholesterolemia per se may cause enhanced fatty streak formation in offspring and whether interventions during pregnancy can reduce it. During pregnancy, 1 group of New Zealand White rabbits was fed control chow and 8 groups were fed hypercholesterolemic diets Chol 1 (yielding plasma cholesterol of 153 mg/dL) or Chol 2 (yielding 359 mg/dL) without or with cholestyramine, vitamin E, or both. Offspring (n=15 to 25 per group) were killed at birth. Maternal hypercholesterolemia enhanced mean lesion size in the aorta of their offspring at birth from 44+/-18x10(3) micrometer(2) per section in controls to 85+/-26x10(3) in Chol 1 and 156+/-49x10(3) in Chol 2 groups (P<0.0001 for both). Cholestyramine or vitamin E treatment of mothers significantly reduced atherosclerosis at birth by up to 39% compared with controls on the same diet. Oxidized fatty acids and malondialdehyde in aortic atherosclerotic lesions and plasma were similarly affected by diets and treatment as atherosclerosis. Our results establish the causal role of hypercholesterolemia and peroxidation in fetal atherogenesis and demonstrate that both lipid-lowering and antioxidant interventions during pregnancy can reduce it. If it can be established that interventions in mothers also affect progression of lesions after birth, this may indicate a novel approach for the prevention of atherosclerosis.

De Novo Expression of Macrophage Migration Inhibitory Factor in Atherogenesis in Rabbits

Abstract: Macrophage migration inhibitory factor (MIF) has been shown to play an important role in macrophage-mediated diseases. We investigate the potential role of MIF in atherogenesis using a hypercholesterolemic rabbit model. New Zealand White rabbits fed with a 2% cholesterol diet developed hypercholesterolemia and early fatty streaks at 1 month. The lesions became advanced at 3 months and were associated with de novo MIF expression by vascular endothelial cells (VECs) and smooth muscle cells (SMCs), as demonstrated by immunohistochemistry, reverse transcriptase-polymerase chain reaction, and in situ hybridization. By contrast, there was no increase in MIF levels in rabbits fed a normal diet. In early atherogenesis, marked upregulation of MIF mRNA and protein by VECs and some intimal cells were closely associated with CD68(+) monocyte adhesion onto and subsequent migration into subendothelial space. Of significance, the accumulation of macrophages was exclusively localized to areas of strong MIF expression, which may be associated with the macrophage-rich fatty streak lesion formation. Upregulation of MIF by SMCs is transient during atherogenesis. Importantly, strong MIF expression by activated macrophages may be responsible for the development of foam cell-rich lesions. Finally, the ability of MIF to induce intercellular adhesion molecule-1 expression by VECs implicates its pathogenic role in atherogenesis. In conclusion, the present study provides the first demonstration that MIF is markedly upregulated during atherogenesis. Upregulation of MIF by VECs and SMCs may play a role in macrophage adhesion, transendothelial migration, accumulation, and, importantly, transformation into foam cells. Furthermore, strong MIF expression by macrophages may both initiate and amplify the atherogenesis process.

Atherogenesis: current understanding of the causes of atheroma

Abstract: U ntil recently, atherosclerosis was thought of as a degenerative, slowly progressive disease, predominantly affecting the elderly, and causing symptoms through its mechanical effects on blood flow, particularly in the small calibre arteries supplying the myocardium and brain. Thus the approach to treatment has traditionally been surgical and focused on the largest and most visible or symptomatic lesions, coupled with a somewhat nihilistic belief that there was little likelihood of medical management affecting such a longstanding “end stage” process. However, recent research into the cellular and molecular events underlying the development and progression of atherosclerosis, prompted by careful descriptive studies of the underlying pathology, has shown that atherosclerosis is a dynamic, inflammatory process that is eminently modifiable. Support for this view comes from clinical trials of lipid lowering agents, particularly the “statins”, which have shown only minor effects on the size of existing lesions, but major reductions in clinical events caused by plaque rupture, implying a beneficial stabilising effect on plaque composition. This calls for a change from a quantitative (how many and how tight are the stenoses?) to a more qualitative (how active are the plaques we cannot see?) approach to atherosclerosis. Also, a better understanding of the molecular and cellular basis of atherosclerosis will inevitably lead to the design of better diagnostic and therapeutic approaches. The purpose of this review is to summarise current understanding of the pathogenesis and progression of atherosclerosis with particular reference to potential new diagnostic or therapeutic approaches. Atherosclerosis begins as a subendothelial accumulation of lipid laden, monocyte derived foam cells and associated T cells which form a non-stenotic fatty streak. With progression, the lesions take the form of an acellular core of cholesterol esters bounded by an endothelialised fibrous cap containing vascular smooth muscle cells (VSMC) and inflammatory cells, predominantly macrophages with some …

Circulating Markers of Inflammation for Vascular Risk Prediction Are they Ready for Prime Time

Abstract: Over the last several years, the idea that inflammation plays a key role in atherosclerosis and its complications has received considerable attention.1 Inflammatory cell infiltration is observed in atherosclerotic plaques at virtually all stages, from the fatty streak to the advanced atheromatous lesions with plaque disruption and thrombosis.1 2 Atherosclerosis is substantially prevented when the biological effects of genes critical for the initiation or maintenance of inflammatory cell recruitment, survival, proliferation, and activation, such as monocyte chemotactic protein-1, interleukin-8, and macrophage colony stimulating factor, are eliminated by gene knockout in atherosclerosis-prone dyslipidemic mice.3 4 5 Similarly, the inhibition of inflammatory signaling pathways mediated by the ligation of CD-40 also results in reduced atherosclerosis in mice.6 Inflammatory cells may also play a key role in promoting plaque disruption by stimulating matrix degradation, inhibiting smooth muscle cell function or survival, and promoting thrombosis by producing tissue factor.2 Similarly, the atheroprotective effects of a variety of interventions such as statins, apolipoprotein A-1/HDL, aspirin, and fibrates are often associated with the evidence of reduced inflammation, further bolstering the notion that inflammation and atherosclerosis are causally related.2 7 8 Although all of the potential triggers of inflammation are not fully known, cytokines, oxidized lipoproteins, and local (arterial) and distant infections (gingivitis, bronchitis) have been implicated.2 9 Early reports from small, randomized trials have shown a reduced clinical event rate with the use of macrolide antichlamydial antibiotics.2 These preliminary observations support the notion that Chlamydia pneumoniae …

Complete Atherosclerosis Regression After Human ApoE Gene Transfer in ApoE-Deficient/Nude Mice

Abstract: —The apolipoprotein E (apoE)-deficient mouse is a relevant animal model of human atherosclerosis. Although the prevention of atherosclerosis development has been documented after somatic gene transfer into animal models, regression of lesions remains to be demonstrated. Thus, we used this genetically defined mouse model nn the nude background to show atherosclerosis regression. ApoE-deficient nude mice were infected with 5×108 or 109 plaque-forming units of a first-generation adenovirus encoding human apoE cDNA. The secretion of human apoE resulted in a rapid decrease of total cholesterol, which normalized the hypercholesterolemic phenotype within 14 days (from 600±100 to 4 months, with a normalization of cholesterol and triglyceride levels during 5 months. At that time, we successfully reinjected the recombinant adenovirus and observed the appearance of the human protein as well as the correction of lipoprotein phenotype. In mice killed 6 months-after the first infection, we observed a dose-dependent regression of fatty streak lesions in the aorta. We showed sustained expression of a transgene with a first-generation adenoviral vector and a correction of dyslipoproteinemia phenotype leading to lesion regression. These data demonstrate that somatic gene transfer can induce plaque regression.

Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions

Abstract: Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.

Endothelial dysfunction and atherosclerosis: Endothelin receptor antagonists as novel therapeutics

Abstract: Atherosclerosis, a chronic systemic disease of the vasculature with an inflammatory component, is the primary cause of cardiovascular morbidity and mortality in industrialized countries [1]. It is associated with the impairment of endothelium-dependent relaxation in the coronary, systemic circulation due to decreased bioavailability of nitric oxide, and increased release oxygen-derived free radicals, thus promoting vasoconstriction, leukocyte adhesion, thrombosis, inflammation, and cell proliferation [2]. Expression of endothelin (ET)-1, a 21-amino acid peptide and major isoform of the endothelin peptide family, is produced by endothelial, vascular smooth muscle cells, and macrophages and acts through Gi-protein-coupled ETA and ETB receptors. Endothelin-1 increases in hypercholesterolemia and atherosclerosis in humans and experimental animals. This paper reviews current experimental and clinical evidence for the involvement of ET-1 in atherogenesis. Furthermore, the effects of ET receptor blockade on experimental hypercholesterolemia and atherosclerosis will be discussed. As chronic endothelin blockade inhibits fatty streak formation and improves vascular function in experimental hypercholesterolemia, hypertension, and heart failure, and as it restores nitric oxide (NO)-mediated endothelial function and reduces atheroma formation in animals with atherosclerosis, endothelin receptor blockade may therefore offer a novel approach for the treatment of atherosclerosis and its vascular complications.

Loss of atheroprotective effect of estradiol in immunodeficient mice.

Abstract: Estradiol significantly decreases fatty streak formation in the aortic root of chow-fed apolipoprotein E-deficient mice. In contrast, immunodeficient mice with homozygous disruption at the recombinase activating gene 2 loci present fatty streak development that is insensitive to estradiol. Lymphocytes thus appear to be required for development of the atheroprotective effect of estradiol in this mouse model.

An overview of the evolution of the atherosclerotic plaque: from fatty streak to plaque rupture and thrombosis.

Abstract: Today, there is a wealth of information concerning the chronology of the cellular and molecular events associated with the development of cardiovascular diseases. It is now clear that atherosclerosis is largerly a result of a dysregulated fibroproliferative inflammatory response [1]. Treatment of cardiovascular disease is rapidly adapting to this new knowledge and the future holds great potential for preventing the disease by blocking the process at multiple stages. This short review provides an overview of the evolution of the atherosclerotic plaque. It focuses of three basic stages of the disease processes: initiation of the fatty streak, transition of the fatty streak to an atheroma, and progression and destabilization of the lesions leading to plaque rupture and occlusive thrombosis. It includes a discussion of the molecular and cellular biology of the atheraogenic process with an emphasis on key molecular mediators of the disease process and provides three tables which list examples of some of the key molecular mediators and the stages in which they are purported to play a role.

Alcohol inhibits the progression as well as the initiation of atherosclerotic lesions in C57Bl/6 hyperlipidemic mice.

Abstract: Background: Evidence that a moderate consumption of alcohol is associated with a reduced incidence of and mortality due to coronary artery disease continues to accumulate. Despite recent evidence that substances in red wine confer resistance to coronary artery disease, it is clear that at least a substantial proportion of the protective effect is due to the alcohol content of the beverage. We have previously shown that the chronic ingestion of alcohol incorporated into a total liquid diet during a 24-week period inhibits the development of fatty streak lesions in hyperlipidemic C57Bl/6 mice. We have now repeated this study and demonstrated that alcohol continues to markedly inhibit atherogenesis during a 48-week period. Methods: Mice were fed a high fat atherogenic liquid diet with 0% or 6% alcohol or a high fat atherogenic pelleted diet with 0% or 15% alcohol in their drinking water. After 24 and 48 weeks on these diets, subgroups of mice were euthanized and the aortas were studied for extent of atherosclerosis. Plasma lipid levels were also measured and flow cytometry studies performed to characterize their T and B lymphocyte populations. Additional groups of mice were given the high fat atherogenic diets for 24 weeks to allow lesions to develop and were then treated with alcohol diets to determine whether they inhibit the progression of the lesions. Results: The alcohol diets suppressed the development of atherosclerotic lesions at both 24 and 48 weeks in both the liquid and pelleted diet models. The addition of the alcohol diets after allowing lesions to form for 24 weeks halted the further progression of the lesions. The alcohol treatments also decreased the plasma levels of total cholesterol and high density lipoprotein (HDL) cholesterol at almost all time intervals. Conclusions: We conclude that alcohol not only inhibits the initial development of atherosclerotic lesions but also inhibits the progression of existing atherosclerotic lesions. The alcohol-mediated decrease in HDL cholesterol in these experiments suggests that HDL plays little or no role in amelioration of atherogenesis in this model.

A new murine model for atherosclerosis with inflammation in the periodontal tissue induced by immunization with heat shock protein 60.

Abstract: It has recently become apparent that the anti-heat shock protein (HSP) antibody plays an important role in the pathogenesis of atherosclerosis. We studied whether immunization with human HSP60 could lead to atherosclerosis in mice. We attempted to induce atherosclerosis in C57BL/6NJcl mice by immunization with human HSP60 under a high-cholesterol diet. The size of fatty streak lesions was significantly enhanced in mice immunized with human HSP60 under a high-cholesterol diet relative to the number in control mice receiving a high-cholesterol diet alone. In addition, these new atherosclerotic model mice showed lesions of inflammation in the periodontal tissue. This new model may thus provide theoretical support for the clinical observation that patients suffering from periodontitis are frequently found to have atherosclerosis. The cytokine ratio of interferon-gamma/interleukin-4 in the high-cholesterol diet group was significantly higher than that in the standard chow group (p<0.05). This suggests the presence of a predominantly Th1-type immune response in atherosclerosis.

Histological and ultrastructural findings suggesting an initiating role for Chlamydia pneumoniae in the pathogenesis of atherosclerosis.

Abstract: AIMS: An association between Chlamydia pneumoniae and atherosclerosis is now well established The finding of C pneumoniae in atherosclerotic lesions has led to the hypothesis that this organism may have an aetiological role in atherogenesis The implications of such a concept are enormous, but to date the pathological features of the lesion have not been examined in the light of this new hypothesis This study was designed to determine the pathological basis of the association between Cpneumoniae and atherosclerotic lesions METHODS: The pathological features of 50 atherosclerotic lesions from 50 different patients, in which Cpneumoniae had been demonstrated by immunocytochemistry and PCR techniques, were examined using light and electron microscopy techniques In 20 cases the lesions were fatty streaks, 20 were fibro-atheroma lesions, and 10 were advanced, complicated lesions RESULTS: Intimal smooth-muscle cells infected with C pneumoniae exhibit vacuolation, loss of myofilaments, an increase in lipid, rupture and fragmentation Macrophages phagocytose these muscle cell fragments, lipid and C pneumoniae Large numbers of extracellular C pneumoniae organisms were identified in the central necrotic core, in areas of fibrosis, in areas of fragmentation of the internal elastic lamina, and in ceroid bodies Neither pathological changes nor organisms were seen in the endothelium CONCLUSIONS : C pneumoniae infection of intimal smoothh muscle cells is accompanied by cytoplasmic alterations and damage The fatty streak appears to be formed by a macrophage response to this muscle damage C pneumoniae is found in early, mature and advanced lesions This is the first study of the pathology of atherosclerosis suggesting that the lesion be interpreted as an infective chlamydial granuloma

Inflammation and infection in acute coronary syndrome.

Abstract: Basic science research has revealed that monocytes and macrophages are important factors in atherogenesis. Immune system activation occurs at all stages of plaque formation, from the fatty streak to an advanced, complicated lesion. The inflammatory response not only stimulates changes in coronary artery endothelial cells causing endothelial injury and dysfunction, but also plays a role in plaque instability and rupture. New perspectives of atherosclerosis and acute coronary syndromes will be discussed in relation to inflammation. In addition, discussion will focus on bacterial and viral infectious microorganisms as a potential factor that may induce and promote inflammation and lead to acute coronary events. Clinical studies in humans have provided insight relating inflammation and infectious agents to atherosclerosis and plaque vulnerability. Other studies focus on specific interventions that may aid in diagnosis and treatment.

Transforming growth factor-01 gene and protein expression associated with atherogenesis of cholesterol-fed rabbits

Abstract: Transfonning growth factor-131 (TGF-131) has been shown to modulate both cell proliferation and the synthesis of extracellular matrix by vascular cells. This study was aimed to establish the temporal correlation between TGF-131 expression, the expression of the extracellular matrix protein fibronectin, and plaque development during atherogenesis of hypercholesterolemic rabbits. New Zealand White rabbits were fed with 2% cholesterol-supplemented chow for 1 week,2 weeks, 3 weeks or 6 weeks. TGF-131 mRNA and protein expression was examined in serial sections of aorta by in situ hybridization and immunohistochemistry. Fibronectin expression was examined by immunohistochemistry. In the control and I-week feeding group, the expression of TGF-Bl mRNA and protein was not apparent. In 2-week feeding group, intimal thickening was detected in which TGF-B 1 mRNA and protein were not clearly observed, either. The 3-week and 6-week feeding groups exhibited fatty streaks in which TGF-Bl rnRNA and protein expression markedly increased as feeding proceeded. Cell typespecific staining indicated that TGF-131 was expressed by macrophages as well as smooth muscle cells of the fatty streaks. Immunostaining of fibronectin detected low expression levels in control, I-week and 2-week feeding groups with pronounced upregulation in the thickened intima and the proximal media in 3-week and 6-week feeding groups. These results implicate a role for TGF-Bl in modulating fatty streak formation and the synthesis of extracellular protein fibronectin during plaque development.

Citrus peel extract as inhibitor of fatty streak formation on the arterial wall

Abstract: Method for inhibiting the formation of fatty streak on the arterial endothelium in a mammal comprise administering a citrus peel extract or citrus peel powder thereto.

Atherogenesis: current understanding of the causes of atheroma.

Abstract: U ntil recently, atherosclerosis was thought of as a degenerative, slowly progressive disease, predominantly affecting the elderly, and causing symptoms through its mechanical effects on blood flow, particularly in the small calibre arteries supplying the myocardium and brain. Thus the approach to treatment has traditionally been surgical and focused on the largest and most visible or symptomatic lesions, coupled with a somewhat nihilistic belief that there was little likelihood of medical management affecting such a longstanding “end stage” process. However, recent research into the cellular and molecular events underlying the development and progression of atherosclerosis, prompted by careful descriptive studies of the underlying pathology, has shown that atherosclerosis is a dynamic, inflammatory process that is eminently modifiable. Support for this view comes from clinical trials of lipid lowering agents, particularly the “statins”, which have shown only minor effects on the size of existing lesions, but major reductions in clinical events caused by plaque rupture, implying a beneficial stabilising effect on plaque composition. This calls for a change from a quantitative (how many and how tight are the stenoses?) to a more qualitative (how active are the plaques we cannot see?) approach to atherosclerosis. Also, a better understanding of the molecular and cellular basis of atherosclerosis will inevitably lead to the design of better diagnostic and therapeutic approaches. The purpose of this review is to summarise current understanding of the pathogenesis and progression of atherosclerosis with particular reference to potential new diagnostic or therapeutic approaches. Atherosclerosis begins as a subendothelial accumulation of lipid laden, monocyte derived foam cells and associated T cells which form a non-stenotic fatty streak. With progression, the lesions take the form of an acellular core of cholesterol esters bounded by an endothelialised fibrous cap containing vascular smooth muscle cells (VSMC) and inflammatory cells, predominantly macrophages with some …