Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth muscle cell proliferation and formation of extracellular matrix in the intima of muscular arteries after vascular injury can lead to severe intimal hyperplasia and stenosis. Cilazapril reduces intimal hyperplasia induced by balloon catheterization of the rat carotid artery by 80%, and significantly decreases the surface area covered by proliferative lesions. We investigated the effects of angiotensin II (A II) on SMC proliferation in cell culture and A-II induction of selected growth factor or growth-related genes in SMC in culture: PDGF A chain, TGF-beta, thrombospondin, c-myc and c-fos, and compared the influence of cilazapril on these responses to A II. A-II induced SMC proliferation, stimulated mRNAs for c-myc and c-fos after 30 min, and stimulated mRNAs for PDGF A chain, TGF-beta, and thrombospondin somewhat later. The ACE inhibitor did not have detectable independent effects on the A-II induced proliferation or gene expression. Thus, these data support the conclusion that cilazapril suppresses SMC proliferation in vivo through the block of conversion of A I to A II, and that A II has a critical and central role in the control of the proliferative response after balloon catheter-induced vascular injury.
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PMID:Cilazapril suppresses myointimal proliferation after vascular injury: effects on growth factor induction in vascular smooth muscle cells. 182 85

To explore the mechanisms by which angiotensin converting enzyme inhibitor (ACEI) prevents the development of left ventricular hypertrophy (LVH), captopril (Cap 100 mg.kg-1/d was administered orally to male spontaneously hypertensive rats from intrauterine period to 16 weeks of age. Male and age-matched untreated WKY rats and SHR were used as controls. Experiments were performed at 40 weeks of age. SBP, left ventricular weight to body weight ratio (LVW/BW), myocardial hydroxyproline (Hypro) and norepinephrine (NE) were determined. The levels of c-myc and c-fos mRNA in the left ventricle were measured by Northern blot. Early-onset Cap therapy significantly decreased SBP at 16 weeks of age. After discontinuance of treatment for 24 weeks, SBP of SHRcap was still maintained at a level lower than that of untreated SHR. LVW/BW and Hypro in SHR cap were markedly reduced. The expression of myocardial c-myc mRNA (n = 5) was decreased by 72% in SHRcap compared with that in the untreated SHR, but the expression of c-fos mRNA (n = 7) and NE was not different between the untreated SHR, SHRcap and WKY rats. These results indicate that early Cap treatment may permanently prevent the development of hypertension, inhibit myocardial hypertrophy (MH), and interstitial fibrosis. Furthermore, the prevention of MH is associated with a decrease in myocardial c-myc mRNA levels, and the development and regression of MH may be irrelevant to proto-oncogene c-fos expression.
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PMID:[Mechanism of inhibition in left ventricular hypertrophy by captopril treatment in spontaneously hypertensive rats]. 776 71

As a consequence of persistently raised blood pressure, left ventricular hypertrophy (LVH) develops as a compensatory mechanism for wall stress induced by the increase in afterload. Recent advances in the fields of molecular biology and genetics are now clarifying the mechanisms involved in the development of LVH. It has been reported that messenger RNA of oncogenes, such as c-fos and c-myc, increases by stretching; these oncogenes contribute to the progression of LVH, the messenger RNA expression of myosin and contractile protein synthesis in the cardiomyocytes. Vasoactive hormones and vascular contracting factors are also reported to have a progressive effect on LVH. In contrast, some antihypertensive agents have been shown to have pharmacological effects on regression of LVH in animals and man. The mechanisms responsible for LVH progression have been extensively studied. In contrast, the mechanisms of LVH regression have not been defined and require elucidation. This paper outlines the basic recognition of the mechanisms of LVH progression and discusses the varied pharmacological actions of calcium antagonists and angiotensin converting enzyme inhibitors on the regression of LVH in man and rats. Although the role of antihypertensive therapy in regression of LVH remains controversial, the calcium antagonist nicardipine appears to have an important role to play in the treatment of LVH in hypertension and in congestive heart failure.
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PMID:Therapeutic advances in the treatment of left ventricular hypertrophy. 837 Mar 75

Although rapid growth of the heart during early postnatal development ceases with maturation of the organism, the potential for cardiomyocyte growth is not lost and may be observed even in senescent hearts. Rapid developmental heart growth is accompanied by a proportional growth of capillaries but not always of larger vessels, and thus coronary vascular resistance gradually increases. Growth of adult hearts can be enhanced by thyroid hormones, catecholamines and the renin-angiotensin system hormones, but these do not always stimulate growth of coronary vessels. Likewise, chronic exposure to hypoxia leads to growth, mainly of the right ventricle and its vessels but without vascular growth elsewhere in the heart. On the other hand, ischaemia is a potent stimulus for the release of various growth factors involved in the development of collateral circulation. Heart hypertrophy develops in response to training, pressure or volume overload. Training usually leads to growth of larger coronary vessels but little growth of capillaries, except in young animals. However, growth of the capillary bed, but not the resistance vasculature capacity, can be induced by either increased coronary blood flow, bradycardia (electrically or pharmacologically induced) or increased inotropism, all of which are involved in the training stimulus. Thus, what actually promotes growth of larger vessels as opposed to capillaries in training is unclear. Pressure overload hypertrophy is mediated by both the renin-angiotensin system and the response of cardiomyocytes to stretch; both lead to activation of early oncogenes (c-fos, c-jun, c-myc) and angiotensin II activates several protein kinases involved in cell growth. In this condition, growth of larger vessels is inadequate, although some capillary growth may occur. Volume overload leads to cardiomyocyte hypertrophy and hyperplasia and some increase in vascular supply. Deficits in capillary supply in pressure or volume overload hypertrophy can be reversed by chronic administration of ACE inhibitors, dipyridamole, the bradycardic drug alinidine or pacing-induced bradycardia respectively, but in neither case is training effective. Mechanical and humoral factors are involved in growth of cardiomyocytes and vessels. For cardiomyocytes, stretch is most important, activating oncogenes, protein kinases and possibly the inositol phosphate pathway, but not ion channels, with regulation by the balance of angiotensin II, TGF-beta 1 and IGF-1, but not FGFs. For vessels, growth is stimulated by stretch and shear stress, possibly with involvement of VEGF. Increased shear stress disrupts the glycocalyx on the luminal side of vessels and releases plasminogen activator and metalloproteinases which disrupt the basement membrane and enable endothelial cell migration and proliferation. It also causes rearrangement of the endothelial cytoskeleton and transmission of mechanical signals to the abluminal side disturbing extracellular matrix and causing distortion of capillary basement membrane. Stretch acting from the abluminal side has a similar effect resulting also in basement membrane disruption and endothelial cell proliferation.
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PMID:Postnatal growth of the heart and its blood vessels. 869 52

A number of data suggest that angiotensin II-dependent activation of the protooncogene c-myc participates in the proliferative response of smooth muscle cells (SMC) of rats with spontaneous hypertension (SHR). We therefore investigated the effects of chronic treatment with the angiotensin converting enzyme (ACE) inhibitor quinapril on the oncoprotein c-Myc and the proliferating cell nuclear antigen cyclin A in SMC of small intramyocardial arteries from the left ventricle of SHR. The expression of c-Myc and cyclin A was assessed by immunocytochemical analysis. The number of smooth muscle cells was assessed by morphometrical analysis. As compared to normotensive Wistar-Kyoto (WKY) rats, untreated SHR exhibited an increased percentages of cells expressing c-Myc (33% +/- 4% v 19% +/- 2%, mean +/- SEM, P < .005) and cyclin A (25 +/- 2 v 11% +/- 1%, P < .001). In quinapril-treated SHR compared with untreated SHR, we found decreased expression of c-Myc (22% +/- 2%, P < .005) and cyclin A (13% +/- 1%, P < .001). No significant differences were found between WKY rats and quinapril-treated SHR in the above parameters. Cyclin A was directly correlated with the number of SMCs in each group of rats. These results suggest that an enhanced expression of c-Myc may be involved in the increased proliferation seen in SMCs from small arteries of SHR. Quinapril administration normalizes proliferation in the SMCs of SHR, possibly by inhibiting the expression of the oncoprotein c-Myc and its effects on the cell cycle.
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PMID:Quinapril inhibits c-Myc expression and normalizes smooth muscle cell proliferation in spontaneously hypertensive rats. 937 Mar 86

To investigate how the interruption of the renin-angiotensin system (RAS) and reduction of blood pressure (BP) affect the lesions of chronic focal and segmental glomerulosclerosis (FGS), we studied the effects of high and low doses of angiotensin-converting enzyme inhibitors (temocapril - TEM) a newly developed ACE inhibitor with biliary tract excretion, on the hypertensive model of FGS. A high dose of TEM significantly lowered BP and suppressed both intense proteinuria and glomerular extracapillary lesions including macrophage infiltration. On the other hand, although a low dose of TEM did not significantly lower BP throughout the experimental period, it prevented renal lesions almost in the same manner as high-dose TEM with suppression of c-myc gene expression in glomeruli. These findings suggest that in PAN-induced chronic FGS, the systemic BP elevation could not be the major factor for the progression of renal damage which TEM could prevent without significant lowering of BP.
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PMID:Significant suppressive effect of low-dose temocapril, an ACE inhibitor with biliary excretion, on FGS lesions in hypertensive rats. 1112 99

Renin-angiotensin system (RAS) in the bone marrow is related to proliferation and cellular differentiation. We investigated the effect of ACE inhibitors (ACEI) captopril (>1mM) and trandolapril (>0.05 mM) and losartan (0.2 mM) on K562 cell line and K562 transfected with c-myc, bcl-x and bcl-2 (KmycB, Kbclx and Kbcl2 respectively). RAS components, proliferation, apoptosis and c-myc expression were analyzed. ACEI and losartan inhibited cell growth, decreased c-myc expression and increased apoptosis. These effects seem to be associated to angiotensin II-induced Smad activation. This work offers a new possible line of treatment for some acute myeloid leukemias and a new area of clinical research.
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PMID:Induction of apoptosis in leukemic cell lines treated with captopril, trandolapril and losartan: a new role in the treatment of leukaemia for these agents. 1901 May 43