Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Much debate surrounds the question of the optimal therapeutic choices for medication to control blood pressure and reduce cardiovascular events. Experimental evidence suggests that drugs that block the renin-angiotensin system retard vascular disease through their direct ability to antagonize the effects of angiotensin II, which has vasoconstrictive, vascular proliferative, and atherosclerotic effects. It is not known how to separate the potential vascular protective effects of the drugs from their antihypertensive benefits. Clinical trial evidence indicates that achieved lower blood pressure goals almost always confer cardiovascular risk reduction advantages. There is also evidence, however, that successful antihypertensive regimens incorporating a renin-angiotensin system blocker, such as an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, provide more cardiovascular risk reduction benefit compared with regimens that do not incorporate a renin-angiotensin blocker. This includes composite or specific end points involving reduction of stroke, myocardial infarction, or development of end-stage renal disease.
 ...
PMID:Providing end-organ protection with renin-angiotensin system inhibition: the evidence so far. 1647 78

The concept of hypertension as primarily a consequence of altered hemodynamics has changed. Many factors are now implicated in the development of hypertensive vascular disease, and the renin-angiotensin-aldosterone system (RAAS) appears to be one of the most significant. Angiotensin II, the principal effector peptide of the RAAS, has far-reaching effects on vascular structure, growth and fibrosis, and is a key regulator of vascular remodeling and inflammation. Reactive oxygen species and a network of signaling pathways mediate angiotensin II and cellular mechanisms that promote remodeling and inflammation. The involvement of aldosterone in vessel-wall and myocardial remodeling has also come under intensive research scrutiny. Treatments that block the pathologic effects of the RAAS at several points have been shown to limit target-organ damage in hypertension and to decrease cardiovascular morbidity and mortality. Understanding the molecular and cellular mechanisms that participate in the early development of hypertensive vascular disease may lead to more targeted treatment and improved outcomes.
 ...
PMID:Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. 1668 92

Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus; up to 80% of deaths in patients with diabetes are closely associated with vascular disease. The ability of the organism to form a collateral network of blood vessels constitutes an important response to vascular occlusive disease and determines to a large part the clinical consequences and severity of tissue ischemia. The development of new vessels is significantly reduced in diabetic patients with coronary or peripheral artery disease. This probably contributes to the severe course of limb ischemia in diabetic patients, in which peripheral artery disease often results in foot ulceration and lower extremity amputation. Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular edema or proliferative diabetic retinopathy. The hallmark of diabetic retinopathy is the lack of microvessels in the macula, leading to hypoxia, associated with peripheral retinal neovascularization that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. The factors that stimulate retinal blood vessel growth have not been fully defined, but there is accumulating evidence that the renin-angiotensin-bradykinin system may be involved in a number of retinal vascular disorders, including retinopathy of prematurity and proliferative diabetic retinopathy. Only a few studies have specifically evaluated the effect of diabetes on angiogenesis in ischemic vascular disease and in the retina. Moreover, the mechanisms by which diabetes could both limit the formation of new blood vessels in most organs and simultaneously induce proliferative diabetic retinopathy remain largely undefined. In the present review, we aimed to briefly describe the main molecular mechanisms involved in the ischemia-induced angiogenesis, and their alterations in diabetes. Possible therapeutic strategies to restore angiogenesis in diabetic patients are also listed.
 ...
PMID:[Diabetes and peripheral arterial occlusive disease: therapeutic potential and pro-angiogenic strategies]. 1670 93

Inflammation is a key mechanism in the initiation, progression, and clinical sequelae of cardiovascular diseases (CVDs), including atherosclerosis, nephropathy, and cardiomyopathy. Angiotensin II, the major effector peptide of the renin-angiotensin-aldosterone system (RAAS), plays a significant role in the advent and perpetuation of these inflammatory diseases, most notably in atherogenesis. Consequently, suppression of the influence of angiotensin II by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may reduce or potentially reverse atherosclerosis and other inflammation-associated CVDs. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors exert anti-inflammatory actions and prevent or reduce the development of atherosclerosis in animal models. Clinically, RAAS suppression reduces common carotid and femoral artery intima-media thickness, thus indicating moderation of the vascular disease process. These clinical benefits likely involve restraint of the deleterious effects of angiotensin II in addition to, or independent of, lowering blood pressure. Increasing evidence that the detection and monitoring of vascular inflammation are important tools in the management of atherosclerosis also implicates the RAAS in this pathogenic process. Inflammatory molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and C-reactive protein have potential diagnostic and prognostic values in CVD and are modified by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Monitoring these markers may be crucial for determining which agents, or combinations of agents, will result in the most clinically beneficial outcomes for patients. Large-scale trials are still required to determine the effects of the long-term suppression of inflammation on CVDs through the use of RAAS modulating agents, as well as to determine how closely markers of inflammatory activity may correlate with CVD outcomes.
 ...
PMID:Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. 1712 70

The main pathologic hallmark of systemic sclerosis (SSc) is endothelial derangement; the pathologic alterations of the vessel wall in SSc are strikingly similar to the modification detected in the atherosclerotic lesions, and it is now evident that SSc is also characterized by accelerated macrovascular disease. Peptides related to angiotensin II, the final product of the renin-angiotensin system (RAS), play a role as regulators of endothelial cell function. Angiotensin-converting enzyme (ACE), the key enzyme in the RAS, is the predominant pathway of angiotensin II formation in blood and tissues. In intron 16 of the gene encoding for ACE an insertion/deletion (I/D) polymorphism, consisting of the presence or absence of a 287-base pair Alu sequence, has been identified. This polymorphism has been related to ACE enzyme levels, and data from experimental studies reported a functional role for this polymorphism in modulating the angiotensin II levels. We previously documented a high ACE D allele frequency in SSc patients and its role in increasing the risk of SSc, thus suggesting that the I/D polymorphism might be a useful genetic marker to identify SSc patients at risk to develop a severe vascular disease, frequently leading to gangrene. Moreover, our preliminary data, besides supporting the role of ACE I/D polymorphism as a predisposing factor to SSc, demonstrated its involvement in accelerated macrovascular disease by increasing the intima media thickness. Therefore, in SSc, not only endothelial dysfunction, but also vascular damage, linked to ACE I/D polymorphism, may significantly contribute to accelerated macrovascular disease, as the ACE D allele, by regulating both the production of angiotensin II and the degradation of bradykinin, contributes to mechanisms involved in the induction and maintenance of vessel wall modification.
 ...
PMID:Angiotensin-converting enzyme in systemic sclerosis: from endothelial injury to a genetic polymorphism. 1685 31

The role of angiotensin II, the key mediator of the renin-angiotensin-aldosterone system, in the pathophysiology of cardiovascular disease is well known. Pharmacologic interruption of the activity of angiotensin II, either through blockade of the angiotensin receptor or inhibition of angiotensin-converting enzyme, is associated with a reduction in cardiovascular disease morbidity and mortality, as evidenced by accumulated data from large-scale, well-controlled clinical trials in high-risk populations. As the underlying mechanisms of vascular disease and the effects of blockade of the renin-angiotensin-aldosterone system on these processes have been further defined, the therapeutic focus has begun to shift toward prevention of disease progression at earlier stages. Continued research has identified early signs of vascular disease, such as endothelial dysfunction and vascular and cardiac remodeling, which occur long before clinical manifestations of cardiovascular disease become evident. Diagnostic tests are now available to assess otherwise healthy individuals for these signs. A preliminary trial is under way to evaluate the role of angiotensin receptor blockade as preventive treatment of individuals with early signs of vascular or cardiac disease.
 ...
PMID:What is the role of angiotensin-receptor blockade in cardiovascular protection? 1707 Jan 45

Hypertension detected in patients with renovascular disease poses a major clinical challenge. The rapid expansion of noninvasive imaging, effective antihypertensive drug therapy, and endovascular interventional procedures combine to make optimal management a moving target. Renal arterial disease accelerates the development of hypertension associated with activation of multiple pressor systems and accelerated target organ injury. Younger individuals with fibromuscular lesions often respond well to renal revascularization with minor associated risks. Care must be taken in cases of complex vascular anomalies, such as renal artery aneurysms. Atherosclerotic renal artery stenosis is detected more commonly than ever before and affects more than 85% of patients referred for revascularization. Most are older patients with long-standing hypertension, diabetes, and pre-existing complications of vascular disease. The benefits of extensive workup and intervention in this group of patients are controversial. Antihypertensive drug therapy is most effectively achieved with drugs that block the renin-angiotensin system, but most require multiple agents. Selection of patients for renal revascularization in this group is far more controversial than with fibromuscular disease. Several small trials failed to identify major benefits with renal artery angioplasty as compared to closely monitored drug therapy, although crossover rates from medical to interventional arms were high. The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) seeks to randomly assign subjects with proven, high-grade renal artery lesions to optimal medical management with and without stenting. This important trial employs distal embolic protection to prevent deterioration of renal function. Understanding the optimal role for renal revascularization depends heavily upon the successful conduct of such trials.
 ...
PMID:Renovascular hypertension update. 1708 62

The clinical importance of renovascular disease, atherosclerotic or of other origin, arises from the fact, that renal artery stenosis (RAS), if hemodynamically significant (> 70% diameter reduction), induces arterial hypertension, renal insufficiency or both. The prevalence of RAS rises with increasing age and with the presence of atherosclerosis of the aorta, carotid, coronary and peripheral arteries. Typical clinical symptoms, as uncontrolled hypertension or renal dysfunction in the absence of pathological urinary findings, are helpful to select patients for further screening methods: We see a prominent role of color duplex sonography as a screening procedure. Intra-arterial angiography remains gold standard for the diagnosis of RAS. The major problem in daily clinical practice is the differentiation between patients in which hypertension and kidney function can be improved or normalized by removal of RAS and those with ''fixed'' hypertension and irreversible kidney dysfunction and therefore to decide if it is worth while to perform invasive treatment as angioplasty or surgery. In this setting, the proof of hemodynamic significance is essential and is indicated especially when the stenosis has a diameter reduction of < 50-70% only. Methods proving a critical stenosis are intra-arterial measurement of the pressure gradient, measurement of differential renal vein renin and duplex sonography. In addition, predictors of treatment outcome should be considered. Studies analyzing if patients improve with blood pressure and kidney function after removal of RAS have shown that high grade stenosis and/or very high blood pressure indicate a good outcome. Further prognostic factors are the absence of parenchymal disease and/or positive functional test. In the presence of a critical stenosis in a patient with a clear clinical problem with hypertension and/or renal dysfunction a positive effect of invasive treatment seems warranted despite the risks that must be considered as well in angioplasty as in surgery. The selection for the type of invasive treatment requires a clarification of the treatment goals in the individual patient, the evaluation of the morphology and localization of the stenosis as the presence of other vascular disease (aortic aneurysm, peripheral artery disease etc.) and the assessment of the risk according to the type of intervention.
 ...
PMID:Renovascular disease: a review of diagnostic and therapeutic procedures. 1712 83

The renin-angiotensin-aldosterone system appears to be one of the key factors in the development of hypertensive vascular disease. Identification of mineralocorticoid receptors in the heart, vasculature, and brain has raised speculation that aldosterone may directly mediate its detrimental effects in these target organs independent of angiotensin II. Aldosterone increases vascular tone due to endothelial dysfunction and enhances the pressor response to catecholamines and up-regulation of angiotensin II receptors. It induces electrolyte transport over the vascular smooth cell membrane and plays a crucial role in vascular remodeling of small and large arteries. Moreover, aldosterone is involved in vascular injury and promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Aldosterone has also been shown to exert a number of effects in the central nervous system. Several human studies have shown that aldosterone is related to baroreflex resetting. Thus, in cases of severe hypertension, there would be fewer compensatory mechanisms to offset blood pressure elevation and ensuing vascular damage. Endothelial and vascular smooth muscle cells have the potential to synthesize aldosterone, and tissue aldosterone could play a more important role in resistant hypertension and target organ damage than circulating aldosterone. Understanding aldosterone synthase polymorphism may provide insight into blood pressure patterns and their consequences. Understanding the vascular mechanisms of aldosterone in resistant hypertension may explain why selective aldosterone receptor blockers might have beneficial effects in resistant hypertension.
 ...
PMID:Aldosterone and the vasculature: mechanisms mediating resistant hypertension. 1721 50

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p<0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p<0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p=0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p<0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p<0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.
 ...
PMID:Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). 1739 2


<< Previous 1 2 3 4 5 6 7 8 9 10