Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy

Department of Physiology and Functional Genomics, College of Medicine, University of Florida, PO Box 100274, Gainesville, FL 32610, USA.
Current Hypertension Reports (Impact Factor: 3.44). 08/2010; 12(4):212-9. DOI: 10.1007/s11906-010-0122-6
Source: PubMed

ABSTRACT A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2-angiotensin (Ang)-(1-7)-Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE-Ang II-angiotensin II type 1 receptor (AT(1)R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2-Ang-(1-7)-Mas counterregulatory axis in PAH is needed.

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Available from: Debra Ely, May 20, 2015
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    • "The promising results of experimental studies on monocrotaline (MCT) or hypoxic rat models with ACE inhibitors (perindopril, captopril) or ARB (losartan, telmisartan) intervention have not been confirmed in clinical trials [71] [72] [73] [74] [75] [76] [77]. Some emphasize the need of further clinic al trials using of subpressor doses of ACE inhibitors or ARBs [63]. Other authors propose another strategy opposite to the pharmacological blockade of RAAS. "
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    • "In addition to contributing to the remodeling process, it results in decreased vasorelaxation of the pulmonary vascular bed. Angiotensin-II also induces vasoconstriction and mitogenesis in PAH, while enhanced expression of the angiotensin-II converting enzyme 2 (ACE2) has been found to have a beneficial effect in animal models of pulmonary hypertension.[1112] "
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