Mechanical load-induced alterations in B-type natriuretic peptide gene expression.
Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide are the known members of the mammalian natriuretic peptide system. Like ANP, BNP is a natriuretic and diuretic hormone that also causes peripheral vasodilation and inhibition of the sympathetic and renin-angiotensin systems. Although originally isolated from porcine brain, the BNP gene is expressed in a specific manner in cardiac myocytes in both the atria and the ventricles, but it is mainly released from the ventricles. The major determinant of BNP secretion is wall stretch, and the levels of BNP mRNA increase substantially in response to cardiac overload. In the clinical setting, BNP appears to be the most powerful neurohumoral predictor of left-ventricular function and prognosis. An acute increase in BNP gene expression occurs within 1 h and mimics the rapid induction of proto-oncogenes in response to hemodynamic stress. BNP can be used as a myocyte-specific marker to identify mechanisms that couple acute mechanical overload to alterations in cardiac gene expression. This paper is focused on the mechanisms that regulate BNP gene expression in cardiac overload. Particularly, autocrine-paracrine factors as well as cytoplasmic signaling pathways and transcription factors involved in mechanical stretch-induced BNP gene expression are discussed.
Tokola
H
H
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
Hautala
N
N
Marttila
M
M
Magga
J
J
Pikkarainen
S
S
Kerkelä
R
R
Vuolteenaho
O
O
Ruskoaho
H
H
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000235:genetics*; D015398:Signal Transduction; D013314:Stress, Mechanical
D020097:Natriuretic Peptide, Brain