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Angiotensin-converting enzyme 2 as a novel target for gene therapy for hypertension. Exp Physiol 2005 May;90(3):299-305

Date

01/11/2005

Pubmed ID

15640278

DOI

10.1113/expphysiol.2004.028522

Scopus ID

2-s2.0-18844381161 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Less than one-third of patients with hypertension have their blood pressures (BP) controlled with current traditional therapeutic approaches for the treatment and control of hypertension. Pharmacological approaches may have reached a plateau in their effectiveness and thus newer innovative strategies need to be studied not only to increase the number of patients that can achieve BP control, but also to find a way to cure, not just manage, the disease. Continuous advances in gene delivery systems coupled with the completion of the Human Genome Project, now make it possible to investigate genetic means for the treatment and possible cure for hypertension. The renin-angiotensin system (RAS) has long been known to regulate BP, and salt and water metabolism. This system is unique in having both a peripheral circulating system and a tissue-based system. Each of these components have been ascribed a variety of physiological effects that have been associated with not only an increase in BP, but also in a variety of the pathophysiological manifestations associated with hypertension, such as cardiac hypertrophy and kidney dysfunction. We and others have used an antisense gene therapy approach, targeting the classical components of the RAS, to effectively attenuate the development of hypertension and related cardiovascular pathophysiologies in numerous experimental models of hypertension. Recently other components of the RAS have been elucidated and some of these components may be potential targets in a gene therapy approach. This article will focus on angiotensin-converting enzyme 2 (ACE2) as a new, potential target of gene therapy for hypertensive disorders.

Author List

Katovich MJ, Grobe JL, Huentelman M, Raizada MK

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carboxypeptidases
Gene Targeting
Genetic Therapy
Humans
Hypertension
Oligonucleotides, Antisense
Peptidyl-Dipeptidase A
Renin-Angiotensin System