Targeting the vasoprotective axis of the renin-angiotensin system: a novel strategic approach to pulmonary hypertensive therapy.
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.
Bradford
Chastity N
CN
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, PO Box 100274, Gainesville, FL 32610, USA. cbradford@ufl.edu
Ely
Debra R
DR
Raizada
Mohan K
MK
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008171:Lung Diseases / Q000188:drug therapy; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2