Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial stiffness is a cardiovascular risk factor that is independent of arterial pressure. Clinically, carotid-femoral pulse wave velocity (PWV) is the gold-standard parameter of arterial stiffness. Recent genetic studies have revealed specific genes that contribute to arterial stiffening. Here we review the recent findings on genome-wide linkage analyses and candidate gene polymorphism association studies. We also focus on the latest advances in the identification of gene variants affecting PWV using high density array single nucleotide polymorphism technology in a recent genome-wide association (GWA) study. Linkage and polymorphism studies revealed a first group of genes affecting the renin-angiotensin-aldosterone system, elastic fibre structural components, metalloproteinases, and the NO pathway. A second group of genes, identified by polymorphism association studies and possibly involved in the pathophysiology of arterial stiffness, includes beta-adrenergic receptors, endothelin receptors, and inflammatory molecules. The last group of genes, identified by GWA studies and unrelated to currently suspected mechanisms of arterial stiffness, may target transcriptional pathways controlling gene expression, differentiation of vascular smooth muscle cells, apoptosis of endothelial cells, or the immune response within the vascular wall.
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PMID:Genetics and pathophysiology of arterial stiffness. 1909 99

Arterial hypertension, insulin resistance, diabetes mellitus are associated with obesity. However exact mechanisms of this association have not been determined yet. Biologically active substances produced by adipose tissue participate in pathogenesis of cardiovascular diseases and complications. In this review we present data on the role of adiponectin -- adipocytokine with unique antiatherogenic, antiinflammatory, and insulin sensitizing properties. Hypoadiponectinemia is considered to be potentially modifiable cardiovascular risk factor and novel therapeutic target. Therapy with PPAR gamma agonists, blockers of renin-angiotensin and sympathetic nervous systems is associated with elevation of concentration of adiponectin.
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PMID:[The role of adiponectin in development and progression of cardiovascular diseases]. 1916 2

Vitamin D is an important prohormone for optimal intestinal calcium absorption for mineralization of bone. Because the vitamin D receptor is present in multiple tissues, there has been interest in evaluating other potential functions of vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional studies have reported that vitamin D deficiency is associated with increased risk of CVD, including hypertension, heart failure, and ischemic heart disease. Initial prospective studies have also demonstrated that vitamin D deficiency increases the risk of developing incident hypertension or sudden cardiac death in individuals with preexisting CVD. Very few prospective clinical studies have been conducted to examine the effect of vitamin D supplementation on cardiovascular outcomes. The mechanism for how vitamin D may improve CVD outcomes remains obscure; however, potential hypotheses include the downregulation of the renin-angiotensin-aldosterone system, direct effects on the heart, and vasculature or improvement of glycemic control. This review will examine the epidemiologic and clinical evidence for vitamin D deficiency as a cardiovascular risk factor and explore potential mechanisms for the cardioprotective effect of vitamin D.
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PMID:Vitamin D deficiency and risk for cardiovascular disease. 1959 2

Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both P<0.0001), with a mean difference between treatment groups of 3.36 g/m(2) (P=0.16). No significant treatment differences were observed in subgroups defined by age, male gender, race, diabetes status, or dose level. However, in female patients, left ventricular mass index reduction was greater with amlodipine/benazepril (P=0.02). Both treatments were well tolerated.
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PMID:Magnetic resonance imaging left ventricular mass reduction with fixed-dose angiotensin-converting enzyme inhibitor-based regimens in patients with high-risk hypertension. 1968 50

The inhibition of renin-angiotensin system (RAS) has an effect beyond reducing blood pressure in the treatment of cardiovascular diseases; it also reduces mortality and morbidity. Although the classic RAS blockage is effective, due to blockage of negative feedback inhibition, it increases plasma renin activity and as a result generates a residual cardiovascular risk. Different from ACE-i and ARB treatments, aliskiren, a direct renin inhibitor, is the only pharmacologic agent that noticeably reduces the plasma renin activity, an independent cardiovascular risk factor. This creates a new option in RAS blockage. The efficacy and safety of aliskiren in the treatment of hypertension has been well established. The effect of aliskiren on cardiovascular mortality and morbidity is being researched. At this point there are many experimental and clinical studies to answer questions on this subject.
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PMID:[Renin and the heart]. 2001 73

The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing of renin-angiotensin-aldosterone system blockers was observed, likely due to protocol exclusion criteria. In conclusion, the NAVIGATOR study comprises prediabetic subjects who typically have concurrent BP and metabolic disturbances and an enhanced risk of CVD, and are thus at higher risk for cardiovascular events than subjects in previous DM prevention trials.
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PMID:Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials. 2018 89

Abdominal obesity is an important cardiovascular risk factor. It is a primary driver of the metabolic syndrome, the cluster of metabolic risk factors that includes insulin resistance and dyslipidemia, and often occurs in association with hypertension. The aim of antihypertensive therapy in patients with metabolic risk factors is to reduce cardiovascular risk, but some antihypertensive agents can exert adverse metabolic effects. For example, beta-blockers produce significant weight gain, and are associated with an increased incidence of diabetes. By contrast, agents that inhibit the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have been shown to be associated with a decreased risk of new-onset diabetes. This reflects the finding that increased activation of the RAS in obese individuals can contribute to the development of the metabolic syndrome. The ARB telmisartan has been shown to act as a selective peroxisome proliferator-activated receptor (PPAR)-gamma modulator. It is known that PPAR-gamma plays a role in the regulation of multiple genes affecting carbohydrate and lipid metabolism; however, the clinical significance of this remains to be established. The potential metabolic effects of RAS blockade should be considered in the choice of antihypertensive therapy for patients with metabolic risk factors, including obesity.
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PMID:Does it matter how blood pressure is lowered in patients with metabolic risk factors? 2040 34

High blood pressure is a major cardiovascular risk factor and its treatment reduces the risk. Five classes of antihypertensive drugs are suitable for the treatment of hypertension either as monotherapy or in some combinations with each other: thiazide and thiazide-like diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. The benefits of antihypertensive treatment are mainly due to lowering of blood pressure and are largely independent of the drug employed. For a given reduction in blood pressure, there is no evidence that "new" antihypertensive agents are superior to "old" agents. In the majority of patients, two or more antihypertensive drugs are required to achieve target blood pressure levels. Preferred drug combinations are diuretics with any of other antihypertensive drugs (with the exception of the combination with beta-blockers in patients at risk of diabetes mellitus), and angiotensin-converting enzyme inhibitors with calcium antagonists. On the other hand, the combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor antagonist should not be employed because of a high incidence of serious adverse renal outcomes. Recently, the first orally active direct renin inhibitor, aliskiren, has been launched for clinical use. The results of ongoing long-term outcome studies will determine the place of aliskiren in the treatment of hypertension.
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PMID:[Antihypertensive drugs in 2010: old and new agents]. 2108 13

Systemic arterial hypertension is a highly prevalent cardiovascular risk factor that causes significant morbidity and mortality, and is becoming an increasingly common health problem because of the increasing longevity and prevalence of predisposing factors such as sedentary lifestyle, obesity and nutritional habits. Further complicating the impact of this disease, mild and moderate hypertension are usually asymptomatic, and their presence (and the subsequent increase in cardiovascular risk) is often unrecognized. The pathophysiology of hypertension involves a complex interaction of multiple vascular effectors including the activation of the sympathetic nervous system, of the renin-angiotensin-aldosterone system and of the inflammatory mediators. Subsequent vasoconstriction and inflammation ensue, leading to vessel wall remodeling and, finally, to the formation of atherosclerotic lesions as the hallmark of advanced disease. Oxidative stress and endothelial dysfunction are consistently observed in hypertensive subjects, but emerging evidence suggests that they also have a causal role in the molecular processes leading to hypertension. Reactive oxygen species (ROS) may directly alter vascular function or cause changes in vascular tone by several mechanisms including altered nitric oxide (NO) bioavailability or signaling. ROS-producing enzymes involved in the increased vascular oxidative stress observed during hypertension include the NADPH oxidase, xanthine oxidase, the mitochondrial respiratory chain and an uncoupled endothelial NO synthase. In the current review, we will summarize our current understanding of the molecular mechanisms in the development of hypertension with an emphasis on oxidative stress and endothelial dysfunction.
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PMID:Oxidative stress and endothelial dysfunction in hypertension. 2151 15

Hypertension is the most common chronic disease in industrialized countries and represents the most common major cardiovascular risk factor after the fifth decade of life in both men and women. The prevalence of hypertension is lower in premenopausal women than men, whereas in postmenopausal women it is higher than in men. Mechanisms responsible for the increase in blood pressure are complex and multifactorial, including loss of estrogen, oxidative stress, endothelial dysfunction, modification in renin-angiotensin system spillover and sympathetic activation. In addition, postmenopausal hypertension can be considered an isolated disease, more typical of elderly women, or part of the metabolic syndrome, which is indeed more common in early postmenopausal women. In particular, metabolic syndrome may be considered a potentially unfavourable prognostic factor in hypertensive postmenopausal women, because it seems to worsen the severity of hypertension and reduce the capacity to respond to specific treatments. This article summarizes the different causes of postmenopausal hypertension and the specific treatment recommended by guidelines for this condition.
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PMID:Hypertension in postmenopausal women: pathophysiology and treatment. 2161 8


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