title: Genetic modification of hypertension by sGCα1.
abstract: Hypertension is an important modifiable risk factor for coronary heart disease, congestive heart failure, stroke, end-stage renal disease, and peripheral vascular disease, but many of the molecular mechanisms and genetic factors underlying the development of the most common forms of human hypertension remain to be defined. Abundant evidence suggests that nitric oxide (NO) and one of its primary targets, the cyclic guanosine monophosphate (cGMP)-generating enzyme soluble guanylate cyclase (sGC), have a critical role in regulating blood pressure. The availability of murine models of hypertension and the revolution in human genetics research (e.g., genome-wide association studies [GWAS]), resulting in the identification of dozens of genetic loci that affect normal variation in blood pressure and susceptibility to hypertension, provide a unique opportunity to dissect the mechanisms by which NO-cGMP signaling regulates blood pressure and to gain important insights into the pathogenesis of hypertension. In this review, we will give an overview of the current knowledge relating to the role of sGC in the regulation of blood pressure, discussing data obtained from genetically modified mouse models as well as from human genetic studies.
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Thier 511B, Boston, MA 02114.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Sips
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase