Genomic and proteomic approaches for targeting of angiotensin-converting enzyme2 for cardiovascular diseases.
OBJECTIVE
Our objective in this review is to summarize current understanding of the role of angiotensin-converting enzyme2 in cardiovascular pathophysiology. In addition, we will present recent advances and future directions in the use of genomic and proteomic approaches for the development of new therapeutic strategies that target angiotensin-converting enzyme2 for cardiovascular diseases.


RESULTS
The angiotensin-converting enzyme homologue, angiotensin-converting enzyme2, plays a central role in counterbalancing the vasoconstrictive, proliferative, and hypertensive peptide, angiotensin II, by generating angiotensin-(1-7), which induces vasodilatory and antiproliferative actions in the cardiovascular system. Gene therapy is a strategy in which a vector is used to deliver beneficial genes systemically or directly into a specific organ. Recent observations suggest that angiotensin-converting enzyme2 overexpression by lentiviral vector-mediated gene delivery leads to an increased local angiotensin-converting enzyme2 expression and evokes protective mechanisms against hypertension and cardiovascular diseases. In addition, endogenous angiotensin-converting enzyme2 activation leads to cardiovascular protection.


CONCLUSIONS
Prevalence of cardiovascular diseases continues to rise in spite of recent success in both the use of combination therapy and introduction of new pharmacotherapeutic agents. Thus, new and innovative approaches must be discovered in order to bring these diseases under control. Angiotensin-converting enzyme2 offers a new target in this regard and the use of state-of-the-art genomic and proteomic-based strategies to target this important member of the renin-angiotensin system holds potential for the development of improved therapeutics for cardiovascular diseases.
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
Anderson J
AJ
Ferreira
Mohan K
MK
Raizada
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000628:therapy; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D040901:Proteomics
D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2