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

Although increased deposition of collagen proteins has been described after myocardial infarction (MI), little is known of time-dependent transcriptional alteration of specific cardiac collagen sub-types as well as the degradative mechanisms for cardiac collagens in right and left ventricular myocardium remote to large left ventricular infarction. We sought to study collagen mRNA abundance and the deposition of specific collagen subtypes in noninfarcted left and right rat heart muscle at different times after MI. We also assessed the activity of different myocardial matrix metalloproteinases (MMP) using zymography to gain some information about degradative pathways for collagen. Furthermore, we assessed passive compliance properties of the right ventricle in experimental hearts. Finally we investigated the role of the renin angiotensin system in the collagen gene expression by administration of an angiotensin converting enzyme (ACE) inhibitor (ramipril) and an angiotensin II receptor type I antagonist (losartan) in experimental animals. We observed that the mRNA abundance of types I and III collagen were increased 3 days after myocardial infarction in both viable left and uninfarcted right ventricular tissues, that they peaked at 7-14 days, and were maintained at relatively high levels in the 28 and 56 days experimental groups. Stiffness of the right ventricular myocardium was significantly increased in the 56 days experimental group when compared to that of control values. These findings correlated with increased immunohistochemical staining patterns of different collagen species in the surviving right (and left) cardiac interstitium of 14, 28, and 56 day experimental cardiac groups. The elevation of fibrillar collagen mRNA abundance in noninfarcted muscle from ventricular chambers was not significantly altered after treatment of experimental animals with ramipril and losartan for up to 14 days. MMP activity was increased in viable left ventricle at 14, 28 and 56 days and at 14 days in the right ventricle in experimental animals when compared to controls. These results indicated that (1) activation of transcription of collagen types I and III gene occurs in acute and chronic MI, and that fibrillar collagen proteins are deposited in the noninfarcted cardiac interstitium after a lag period relative to increased corresponding mRNA abundance; (2) an increase in MMP activity in chronic experimental hearts indicates that increased collagen deposition may be due to an increment in collagen synthesis rather by reduced degradation of collagen, and that MMP activation may be important in remodeling of the noninfarcted cardiac stroma; (3) an increase of right ventricular stiffness was associated with increased deposition of collagen; (4) as losartan treatment is not associated with any normalization of elevated collagen mRNA abundance, the upregulation of collagen gene expression in this model is not mediated by AT1 receptor; and (5) the reduction of cardiac fibrosis mediated by ACE inhibition and losartan treatment may reside at the post-translational level in cardiac collagen metabolism.
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PMID:Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction. 897 79

Epidemiological studies have demonstrated that pulse pressure and arterial stiffness are strong independent risk factors for all-cause and cardiovascular mortality, primary coronary heart disease (CHD) and stroke. Thus, treatment of hypertension and congestive heart failure (CHF) should aim to reduce arterial stiffness in order to lower afterload and pulse pressure, promote regression of left ventricular and arterial wall hypertrophy and, in CHF, increase cardiac output. Elevation of diastolic blood pressure appears to be beneficial to coronary perfusion and this may be particularly relevant in the setting of CHD. In patients with essential hypertension, numerous studies have shown a decrease in arterial stiffness with various pharmacological classes of antihypertensive agents (including beta-blockers, diuretics, ACE inhibitors, angiotensin II receptor antagonists and calcium antagonists), either acutely or during long-term studies. Their efficacy is not surprising, since blood pressure reduction unloads the stiff components of the arterial wall, such as collagen. However, it seems likely that pharmacological treatment has the capacity to decrease arterial stiffness beyond blood pressure reduction, because long-term drug administration can modify the wall components, including a reduction in collagen density or changes in the spatial arrangement of the wall materials. Whether classes of antihypertensive agents vary in their efficacy to affect arterial structure and thus influence arterial stiffness via a pressure-independent mechanism is more controversial and has yet to be evaluated in large-scale trials. A Consensus Conference on the 'Clinical Applications of Arterial Stiffness', held in Paris, June 17, 2000, recommended guidelines for further pharmacological and therapeutic studies on arterial stiffness. Among them were the following: 'To reach full normalisation of arterial stiffness, pharmacological and therapeutic trials should aim at lowering systolic and diastolic blood pressure to a larger extent than in previous studies and giving treatments for a longer duration than in most previous studies;Mainly, studies designed to demonstrate the prognostic value of the reduction of arterial stiffness are urgently needed. They should be performed in patients at high cardiovascular risk, on a large scale and a long-term basis, and include all-cause and cardiovascular mortality and cardiovascular morbidity'.
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PMID:[Drugs and arterial stiffness in hypertensive patients]. 1270 78

The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the <<elasticity>> of artery as a hollow structure, the elastic incremental modulus (Einc) characterizes the properties of the arterial wall biomaterials, independently of vessel geometry. As an alternative, arterial D can be evaluated by measuring the pulse wave velocity (PWV) which increases with the stiffening of arteries. Arterial stiffening increases left ventricular (LV) afterload and alters the coronary perfusion. With increased PWV, the WR impacts on the aorta during systole, increasing systolic pressures and myocardial oxygen consumption, and decreasing diastolic BP and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix (arteriosclerosis) as classically observed during aging or in arterial hypertension. The arterial stiffening estimated by changes in aortic PWV and intensity of WR are independent predictors of survival in end stage renal disease (ESRD) and general population. Improvement of arterial stiffening could be obtained by antihypertensive treatmen as observed with the calcium-channel blocker and ACE inhibitors. ACE inhibitors increased AC and reduced WR, and it has been shown that reversibility of aortic stiffening and use of ACE inhbitors had favorable independent effect on survival in hypertensive patients with advanced renal disease.
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PMID:Arterial stiffness: pathophysiology and clinical impact. 1570 23

Cross-sectional studies have shown a positive association between increased pulse pressure (PP) and an increased likelihood of a C-reactive protein (CRP) level >3 mg/L. In a retrospective subgroup analysis of the hypertensive subjects of the multicenter double-blind study, REASON (PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd), in which fixed first-line antihypertensive combination therapy with an angiotensin converting enzyme (ACE) inhibitor, perindopril (2 mg), and a diuretic, indapamide (0.625 mg), proved significantly more effective than atenolol in normalizing PP, we sought to determine whether perindopril plus indapamide was also more effective than atenolol in lowering CRP levels and, if so, whether this effect correlated with a preferential reduction in PP. At the final visit (12 months) in the 269 patients studied, the decrease in PP was greater, and the proportion of patients with CRP >3 mg/L lower (17.9% versus 28. 9%, P=0.03; adjusted odds ratio, 1.02 to 4.08, P=0.01), in the perindopril plus indapamide group than in the atenolol group. After adjustment for confounders, patients with a baseline CRP >3 mg/L displaying the greatest decrease in PP were more likely (P=0.04) to have a CRP < or =3 mg/L at 12 months. No such relationship was found with systolic or diastolic blood pressure. Perindopril-indapamide combination therapy is more effective than beta-blockade in lowering elevated CRP in hypertensive subjects. This effect is significantly associated with a more effective PP reduction in patients with baseline CRP >3 mg/L.
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PMID:C-reactive protein elevation predicts pulse pressure reduction in hypertensive subjects. 1595 15

Biomechanical properties of osteotomies and physiologically fractured canine femurs fixed with six-hole stainless steel AO/DCP plates (Synthes: Paoli, PA) were investigated with torsional loading 12 weeks postoperatively and were compared. Biomechanical evaluation of fracture healing with compression plate fixation requires a well controlled fracture creation technique which should reflect closely the natural process. Osteotomy has been suspected of creating ;local bone necrosis, a segmental defect, and subsequent healing patterns which do not mimic those following a more physiologic fracture. Two fracture techniques were compared in the mid-diaphyseal canine femur. An osteotomy was created in one limb and stabilized with a dynamic compression plate, while the contralateral limb was fractured physiologically utilizing four-point bending (modified technique of Ashhurst et al.) and also stabilized with a dynamic compression plate. Comminution developed in one animal during the four-point bending fracture creation technique and nonunion developed in an animal following osteotomy. Following sacrifice at three months, dynamic torsion testing demonstrated no statistical difference in mean torque to failure (osteotomy = 27.7, SD 9.4 N m; physiologic fracture = 28.4, SD 5.0 N m). Stiffness, rotation to failure, and energy to failure were also analysed and demonstrated no statistical difference.
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PMID:Biomechanics of healed experimental fractures. 2391 80