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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.
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PMID:Angiotensin-converting enzyme 2 is an essential regulator of heart function. 1207 31

Cardiovascular disease is predicted to be the commonest cause of death worldwide by the year 2020. Diabetes, smoking and hypertension are the main risk factors. The renin-angiotensin system plays a key role in regulating blood pressure and fluid and electrolyte homeostasis in mammals. The discovery of specific drugs that block either the key enzyme of the renin-angiotensin system, angiotensin-converting enzyme (ACE), or the receptor for its main effector angiotensin II, was a major step forward in the treatment of hypertension and heart failure. In recent years, however, the renin-angiotensin system has been shown to be a far more complex system than initially thought. It has become clear that additional peptide mediators are involved. Furthermore, a new ACE, angiotensin-converting enzyme 2 (ACE2), has been discovered which appears to negatively regulate the renin-angiotensin system. In the heart, ACE2 deficiency results in severe impairment of cardiac contractility and upregulation of hypoxia-induced genes. We shall discuss the interplay of the various effector peptides generated by angiotensin-converting enzymes ACE and ACE2, highlighting the role of ACE2 as a negative regulator of the renin-angiotensin system.
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PMID:Just the beginning: novel functions for angiotensin-converting enzymes. 1241 8

The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only known human homologue of the key regulator of blood pressure angiotensin-converting enzyme (ACE). Since its discovery in 2000, ACE2 has been implicated in heart function, hypertension and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin II to angiotensin-(1-7). Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts.
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PMID:ACE2: from vasopeptidase to SARS virus receptor. 1516 41

Recent intriguing findings from genetic linkage, knockout, and physiologic studies in mice and rats led us to conduct the first investigation of the novel angiotensin-converting enzyme 2 gene (ACE2) in human hypertension (HT). We genotyped four single nucleotide polymorphisms (SNP) (A-->G at nucleotide 1075 in intron 1, G-->A at nucleotide 8790 in intron 3, C-->G at nucleotide 28330 in intron 11, and G-->C at nucleotide 36787 in intron 16) in HT (n = 152) and normotensive (NT, n = 193) groups having inherently high biological power (>80%) due to our inclusion only of subjects whose parents had the same BP status as themselves. The SNPs were in linkage disequilibrium (D' = 54% to 100%, P =.05 to 0.0001). Because ACE2 is on the X chromosome, data for each sex were analyzed separately. Minor allele frequencies in HT versus NT were as follows: for the intron 1 variant 0.21 versus 0.17 in female subjects (P =.31) and 0.25 versus 0.29 in male subjects (P =.60); intron 3 variant 0.22 versus 0.18 in female subjects (P =.35) and 0.15 versus 0.20 in male subjects (P =.47); intron 11 variant 0.39 versus 0.46 in male subjects (P = 0.17) and 0.31 versus 0.30 in male subjects (P =.96); intron 16 variant 0.20 versus 0.19 in female subjects (P =.72) and 0.17 versus 0.17 in male subjects (P =.95). Haplotype analysis was also negative. These data provide little support for ACE2 in genetic predisposition to HT.
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PMID:No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension. 1523 82

There is increasing evidence that all-trans retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. To further validate effects of atRA on the RAS and to assess the possibility that atRA affects the activity of angiotensin-converting enzyme 2 (ACE2), gene, and protein expression of ACE2 have been examined by real-time polymerase chain reaction and Western blot methods in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats were treated with atRA (10 or 20 mg x kg(-1) x day(-1)) or placebo given as daily intraperitoneal injection for 1 month. ACE2 expression was markedly decreased in placebo-treated SHR when compared with WKY rats. However, in atRA-treated SHR, a significant upregulation of ACE2 expression was observed in heart and kidney. In conclusion, chronic atRA treatment increases gene and protein expressions of ACE2, resulting in the reduction of blood pressure and the attenuation of myocardial damage in SHR, which suggests that atRA may be an attractive candidate for the potential prevention and treatment of human essential hypertension.
Hypertension 2004 Dec
PMID:Upregulation of angiotensin-converting enzyme 2 by all-trans retinoic acid in spontaneously hypertensive rats. 1547 83

Less than one-third of patients with hypertension have their blood pressures (BP) controlled with current traditional therapeutic approaches for the treatment and control of hypertension. Pharmacological approaches may have reached a plateau in their effectiveness and thus newer innovative strategies need to be studied not only to increase the number of patients that can achieve BP control, but also to find a way to cure, not just manage, the disease. Continuous advances in gene delivery systems coupled with the completion of the Human Genome Project, now make it possible to investigate genetic means for the treatment and possible cure for hypertension. The renin-angiotensin system (RAS) has long been known to regulate BP, and salt and water metabolism. This system is unique in having both a peripheral circulating system and a tissue-based system. Each of these components have been ascribed a variety of physiological effects that have been associated with not only an increase in BP, but also in a variety of the pathophysiological manifestations associated with hypertension, such as cardiac hypertrophy and kidney dysfunction. We and others have used an antisense gene therapy approach, targeting the classical components of the RAS, to effectively attenuate the development of hypertension and related cardiovascular pathophysiologies in numerous experimental models of hypertension. Recently other components of the RAS have been elucidated and some of these components may be potential targets in a gene therapy approach. This article will focus on angiotensin-converting enzyme 2 (ACE2) as a new, potential target of gene therapy for hypertensive disorders.
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PMID:Angiotensin-converting enzyme 2 as a novel target for gene therapy for hypertension. 1564 Feb 78

Hypertension afflicts over 65 million Americans and poses an increased risk for cardiovascular morbidity such as stroke, myocardial infarction and end-stage renal disease resulting in significant mortality. Overactivity of the renin-angiotensin system (RAS) has been identified as an important determinant that is implicated in the etiology of these diseases and therefore represents a major target for therapy. In spite of the successes of drugs inhibiting various elements of the RAS, the incidence of hypertension and cardiovascular diseases remain steadily on the rise. This has lead many investigators to seek novel and innovative approaches, taking advantage of new pathways and technologies, for the control and possibly the cure of hypertension and related pathologies. The main objective of this review is to forward the concept that gene therapy and the genetic targeting of the RAS is the future avenue for the successful control and treatment of hypertension and cardiovascular diseases. We will present argument that genetic targeting of angiotensin-converting enzyme 2 (ACE2), a newly discovered member of the RAS, is ideally poised for this purpose. This will be accomplished by discussion of the following: (i) summary of our current understanding of the RAS with a focus on the systemic versus tissue counterparts as they relate to hypertension and other cardiovascular pathologies; (ii) the newly discovered ACE2 enzyme with its physiological and pathophysiological implications; (iii) summary of the current antihypertensive pharmacotherapy and its limitations; (iv) the discovery and design of ACE inhibitors; (v) the emerging concepts for ACE2 drug design; (vi) the current status of genetic targeting of the RAS; (vii) the potential of ACE2 as a therapeutic target for hypertension and cardiovascular disease treatment; and (viii) future perspectives for the treatment of cardiovascular diseases.
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PMID:ACE2: A novel therapeutic target for cardiovascular diseases. 1600 3

This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-7) as a hormone that, in its own right, opposes the vasoconstrictor and proliferative actions of angiotensin II. The work discussed here additionally analyzes the newest findings on angiotensin-converting enzyme 2, the angiotensin-converting enzyme homologue that efficiently hydrolyzes angiotensin II into angiotensin-(1-7). Both components of this system may significantly influence our future perspective of the role of the renin-angiotensin system, not just in terms of its role in the regulation of cardiovascular and renal function but, moreover, as regulators of a vast array of disease processes in which inflammation and immune mechanisms play a role.
Hypertension 2006 Mar
PMID:Angiotensin-converting enzyme 2 and angiotensin-(1-7): an evolving story in cardiovascular regulation. 1636 92

To establish whether angiotensin-converting enzyme 2 (ACE2) gene A/G single nucleotide polymorphism is associated with hypertension in Chinese patients with metabolic syndrome. The study was conducted in 353 patients with metabolic syndrome. The alleles of the ACE2 A/G polymorphism, which is located on the X chromosome, were detected using polymerase chain reaction and subsequent cleavage by Alu I restriction endonuclease. G allele frequencies in patients with metabolic syndrome were 36.6% in female subjects and 43.4% in male subjects, respectively. Female patients with metabolic syndrome who carry the GG genotype had a significantly higher diastolic blood pressure compared with other genotypes. Multivariate logistic regression showed that female gender (P = 0.019) and carrying only the G allele (odds ratio 2.83 [95% CI 1.36 to 5.91]; P = 0.005) were significantly associated with increased diastolic blood pressure. It is concluded that the ACE2 A/G polymorphism is associated with hypertension in patients with metabolic syndrome.
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PMID:Association of angiotensin-converting enzyme 2 gene A/G polymorphism and elevated blood pressure in Chinese patients with metabolic syndrome. 1645 67

Hypertension is often associated clinically with diabetes as part of the insulin-resistance syndrome or as a manifestation of renal disease. Elevated systemic blood pressure accelerates micro- and macrovascular complications in diabetes. Vasoactive hormone pathways including the renin-angiotensin-aldosterone system (RAAS) appear to play a pivotal role in the pathogenesis and progression of diabetic complications and possible diabetes itself. Recent studies have increased our understanding of the complexity of the RAAS with identification of new components of this cascade including angiotensin-converting enzyme 2 and a putative renin receptor. Agents that interrupt the RAAS confer end-organ protection in diabetes via hemodynamic and non-hemodynamic mechanisms. Trials are investigating the possible role of RAAS blockade in the prevention of type 2 diabetes.
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PMID:Hypertension and diabetes: role of the renin-angiotensin system. 1695 81


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