Circulation research
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Circulation research · May 2020
ReviewAngiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2.
ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. ⋯ The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.
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Circulation research · Jan 2020
Randomized Controlled Trial Comparative StudyVitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence.
Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. ⋯ Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259.
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Circulation research · Oct 2019
ADAMTS8 Promotes the Development of Pulmonary Arterial Hypertension and Right Ventricular Failure: A Possible Novel Therapeutic Target.
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with aberrant pulmonary artery smooth muscle cells (PASMCs) proliferation, endothelial dysfunction, and extracellular matrix remodeling. ⋯ These results indicate that ADAMTS8 is a novel therapeutic target in PAH.
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Circulation research · Jul 2019
Impact of the 2017 ACC/AHA Guideline for High Blood Pressure on Evaluating Gestational Hypertension-Associated Risks for Newborns and Mothers.
In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) released a new hypertension guideline for nonpregnant adults, using lower blood pressure values to identify hypertension. However, the impact of this new guideline on the diagnosis of gestational hypertension and the associated maternal and neonatal risks are unknown. ⋯ Adopting the 2017 ACC/AHA guideline would result in a substantial increase in the prevalence of gestational hypertension; subclinical blood pressure elevations during late pregnancy were not associated with increased maternal and neonatal risk in this cohort. Therefore, the 2017 ACC/AHA guideline may improve the detection of high blood pressure during pregnancy and the efforts to reduce maternal and neonatal risk. Replications in other populations are required.
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Circulation research · Jun 2019
Macrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating Inflammation.
TGF (transforming growth factor)-β is critically involved in myocardial injury, repair, and fibrosis, activating both Smad (small mothers against decapentaplegic)-dependent and non-Smad pathways. The in vivo role of TGF-β signaling in regulation of macrophage function is poorly understood. We hypothesized that in the infarcted myocardium, activation of TGF-β/Smad signaling in macrophages may regulate repair and remodeling. ⋯ We demonstrate that Smad3 critically regulates function of infarct macrophages, by mediating acquisition of a phagocytic phenotype and by contributing to anti-inflammatory transition. Smad3-dependent actions in macrophages protect the infarcted heart from adverse remodeling.