title: ACE2, a promising therapeutic target for pulmonary hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a chronic lung disease with poor diagnosis and limited therapeutic options. The currently available therapies are ineffective in improving the quality of life and reducing mortality rates. There exists a clear unmet medical need to treat this disease, which necessitates the discovery of novel therapeutic targets/agents for safe and successful therapy. An altered renin-angiotensin system (RAS) has been implicated as a causative factor in the pathogenesis of PAH. Angiotensin II (Ang II), a key effector peptide of the RAS, can exert deleterious effects on the pulmonary vasculature resulting in vasoconstriction, proliferation, and inflammation, all of which contribute to PAH development. Recently, a new member of the RAS, angiotensin converting enzyme 2 (ACE2), was discovered. This enzyme functions as a negative regulator of the angiotensin system by metabolizing Ang II to a putative protective peptide, angiotensin-(1-7). ACE2 is abundantly expressed in the lung tissue and emerging evidence suggests a beneficial role for this enzyme against lung diseases. In this review, we focus on ACE2 in relation to pulmonary hypertension and provide proof of principle for its therapeutic role in PAH.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Shenoy
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000517:prevention & control; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018384:Oxidative Stress; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000502:physiology*; D020257:Ventricular Remodeling
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2