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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vascular endothelium plays a vital role in the control of the circulation. It metabolizes various vasoactive substances, coverts angiotensin I to angiotensin II and secretes the potent vasodilators prostacyclin and EDRF (NO) and the vasoconstrictor peptide endothelin-1. The balance between these mediators determines the responses of the cardiovascular system in diseases such as hypertension, atherosclerosis and myocardial infarction.
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PMID:The Croonian Lecture, 1993. The endothelium: maestro of the blood circulation. 814 36

Proliferation of smooth muscle cells within the intima plays a key role in vascular occlusive disorders such as atherosclerosis and restenosis following balloon angioplasty. Among the factors that may be important in the development of vascular lesions, several authors have reported that the local angiotensin system participates in modulating the proliferation of smooth muscle cells after arterial injury. This study was therefore designed to characterize the antagonistic properties and to investigate the antiproliferative effect of a newly developed non-peptide angiotensin II AT1 receptor antagonist, SR 47436. This compound is a potent and competitive antagonist of the binding of [125I]angiotensin II to its receptor on cultured human aortic smooth muscle cells, exhibiting an IC50 value of 1.7 +/- 0.6 nM. SR 47436 was 10-fold more potent than DuP 753 (Losartan) (IC50 = 20.8 +/- 3.7 nM). In these same cells, SR 47436 potently inhibited the angiotensin II-induced [Ca2+]i increase (IC50 = 0.53 +/- 0.13 vs. 7.4 +/- 1.3 nM for DuP 753). Angiotensin II is a potent mitogen for human aortic smooth muscle cells in culture, exhibiting a maximum proliferative response at 1 microM. SR 47436 and Losartan prevented angiotensin II-induced proliferation of these cells in a dose-dependent manner (IC50 = 0.32 +/- 0.09 and 0.71 +/- 0.08 microM, respectively). SR 47436 displayed a marked in vitro inhibition of serum-induced smooth muscle cell proliferation (IC50 = 5.5 +/- 0.8 microM). A selective AT2 receptor antagonist, PD 123177 did not affect angiotensin II-induced responses in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro. 814 71

Based upon literature the renin-angiotensin system involvement in the pathogenesis of atherosclerosis has been discussed. Angiotensin II leads to the increased production of growth factors such as PDGF, TGF-beta, FGF and extracellular matrix proteins. There are evidences that angiotensin II stimulates expression of egr-1, c-jun, c-fos and c-myc oncogenes in vascular smooth muscle cells. Proliferation of aortic smooth muscle cells in response to the injury can be reduced by inhibitors of renin-angiotensin system what supports the hypothesis that angiotensin II can contribute to the pathogenesis of atherosclerosis.
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PMID:[Renin-angiotensin system and atherosclerosis]. 820 30

While the circulating renin-angiotensin system (RAS) plays an important role in short-term maintenance of cardiovascular homeostasis, recent studies point to a role in long-term cardiovascular regulation for endogenous RAS in target tissues. This article focuses on the multiple effects of tissue angiotensin enzyme (ACE) and angiotensin II (Ang II), its active peptide product. Ang II has been shown to be a potent growth factor in vascular smooth muscle cells. Depending on the local conditions, the vascular response may be either hypertrophy or hyperplasia. The molecular mechanisms involved in the interactions of Ang II with endothelium- and smooth muscle-derived cell products may play important roles in the modulation of vascular structure in hypertension and vascular injury. Evidence also points to a role for Ang II in the development of left ventricular hypertrophy in hypertension. In addition, cardiac RAS may contribute to the pathophysiology of heart failure. Experimental and clinical studies with ACE inhibitors point to a role for tissue ACE activity in the development of atherosclerosis, as well as cardiac hypertrophy and remodeling.
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PMID:Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart. 839 69

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.
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PMID:Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. 856 68

Angiotensin II (Ang II) raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Ang II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT1), and may be blocked by losartan, a specific blocker of AT1 receptors. In particular, studies employing losartan have shown that Ang II is an important contributor to BP regulation and plays a significant role in hypertension and in the pathophysiology of vascular damage during the course of hypertension. Ang II is also involved in the process of atherosclerosis and in remodelling and repair processes of the myocardium following myocardial infarction. Finally, increased Ang II is an important part of neurohumoral activation in heart failure. Exciting new discoveries concerned with polymorphisms of genes coding for angiotensin converting enzyme (ACE) and angiotensinogen suggest that Ang II may be genetically associated with increased risk for myocardial infarction, hypertension and left ventricular hypertrophy.
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PMID:Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. 858 76

The type I cGMP-dependent protein kinase (cGK) is one of the major pathways for the cGMP cascade and has been demonstrated to inhibit platelet aggregation, relax smooth muscle cells, and control cardiocyte contractility. There are two subtypes of the type I cGK, cGKIalpha and cGKIbeta. The former is more sensitive to cGMP than the latter. In humans, cGKIbeta cDNA was isolated, but the full structure and tissue-specific gene expression of cGKIalpha have not been determined. The significance of cGK in human cardiovascular diseases has not been investigated at the molecular level. In the present study, we isolated the full-length human CGKIalpha cDNA (-36 to +2177; the translation start site: +1) enclosing the 671-amino acid protein. Nucleotides +267 to +2177 of the isolated cDNA were identical to the corresponding nucleotides of human cGKIbeta cDNA. Southern blot analysis suggested that human cGKIalpha and cGKIbeta are generated by alternative splicing of a single gene assigned to chromosome 10. By Northern blot analysis, we detected abundant human cGKIalpha mRNA (7.0 kb) in the aorta, heart, kidneys, and adrenals. In contrast, human cGKIbeta mRNA (7.0 kb) was detected abundantly only in the uterus. In cultured vascular smooth muscle cells, the type I cGK mRNA concentration was reduced to 10% of the basal level by 4 x 10(-10) mol/L platelet-derived growth factor. Angiotensin II (10(-8) mol/L), transforming growth factor-beta (4 x 10(-11) mol/L), and tumor necrosis factor-alpha (6 x 10(-6) mol/L) also exhibited an inhibitory effect on type I cGK gene expression. These findings suggest a pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis.
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PMID:cDNA cloning and gene expression of human type Ialpha cGMP-dependent protein kinase. 861 2

In the present study, we examined the effect of angiotensin II (Ang II) on phosphatidylcholine-hydrolyzing phospholipase D activity in subcultured rat aortic smooth muscle cells (SMC). Ang II dose-dependently stimulated the formation of choline and inositol phosphates. The effect of Ang II on the formation of inositol phosphates (EC50 was 0.249 +/- 0.091 nM) was more potent than that on the formation of choline (EC50 was 2.39 +/- 1.29 nM). A combination of Ang II and 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, additively stimulated the formation of choline. Staurosporine, an inhibitor of protein kinases, inhibited the TPA-induced formation of choline, but had little effect on the Ang II-induced choline formation. Ang II stimulated Ca2+ influx from extracellular space time- and dose-dependently. The depletion of extracellular Ca2+ by (ethylenebis(oxyethylenenitrilo)) tetraacetic acid (EGTA) significantly reduced the Ang II-induced formation of choline. Genistein and tyrphostin, protein tyrosine kinase inhibitors, significantly suppressed the Ang II-induced Ca2+ influx. Genistein and tyrphostin also suppressed the Ang II-induced formation of choline. These results suggest that Ang II stimulates phosphatidylcholine-hydrolyzing phospholipase D due to Ca2+ influx from the extracellular space in rat aortic SMC, and that protein tyrosine kinase is involved in the Ang II-induced Ca2+ influx, resulting in the promotion of phosphatidylcholine hydrolysis.
Atherosclerosis 1996 Mar
PMID:Tyrosine kinase is involved in angiotensin II-stimulated phospholipase D activation in aortic smooth muscle cells: function of Ca2+ influx. 867 16

Angiotensin II (AII) is recognized as being an important factor in the pathogenesis of hypertension and atherosclerosis. Monocyte binding to affected endothelial cells is one of the earliest features of atherosclerosis. However, the effect of AII on monocyte binding has not been fully studied. Treatment of human aortic endothelial cells (HAEC) and rabbit aortic endothelial cells (RAEC) for 18 hours with AII induced the adhesion of monocytes but not neutrophils to these cells. This induction was reduced by inhibitors of AII receptors (Type I and Type II). Angiotensin II-induced monocyte binding was not associated with induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), or intercellular adhesion molecule-1 (ICAM-1). These results suggest that AII can accelerate the rate of atherosclerosis by increasing monocyte binding to the endothelium.
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PMID:Angiotensin II increases monocyte binding to endothelial cells. 883 2

It is recognized that heart failure in patients with atherosclerotic lesion is the result of ischemia. However, there may also be cardiac cell dysfunction independent of ischemia, as factors advancing both of atherosclerosis and heart failure are discovered. The renin-angiotensin system is one of factor and angiotensin-converting enzyme inhibitor (ACEi) prevents progression of atherosclerotic lesion and heart failure. To elucidate the association of atherosclerosis and cardiac cell dysfunction, we investigated the effects of ACEi on cultured cardiac myocytes. Captopril increased beta-receptor density of myocytes and augmented the response to isoproterenol. CV-3480, a ACEi, also up-regulated beta-receptors but angiotensin I, angiotensin II and angiotensin type I receptor antagonist did not. Bradykinin B2 receptor blocker, HOE140, suppressed the effect of captopril on cultured cells. The results suggest that ACEi up-regulated beta-receptors and augmented the response to beta-receptor agonist through BK potentiation.
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PMID:[Association of atherosclerosis and cardiac cell dysfunction]. 895 33


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