title: Lack of S100A1 in mice confers a gender-dependent hypertensive phenotype and increased mortality after myocardial infarction.
abstract: S100A1 is a small Ca(2+)-binding protein expressed in the myocardium and blood vessels that is downregulated in the diseased heart and plays a role in the regulation of cardiac muscle Ca(2+) homeostasis and contractility. To understand its physiological role under basal conditions and after myocardial infarction (MI), we used a mouse strain with targeted deletion of the S100A1 gene [S100A1 knockout (KO) mice]. We compared 49 wild-type (WT) and 56 S100A1 KO mice (6-8 wk old) over 28 days after MI with sham-operated controls. We also examined the effect of S100A1 deficiency on vascular function of isolated blood vessels. S100A1 KO mice demonstrated worse survival compared with WT mice (21% vs. 69%, respectively, P < 0.001). Hemodynamic evaluation revealed a higher mean arterial pressure (MAP) in sham-operated KO animals compared with WT animals (99 +/- 4 vs. 77 +/- 3 mmHg, respectively, P < 0.001) that persisted in both groups after MI (86 +/- 2 vs. 66 +/- 4 mmHg, respectively, P < 0.001). Sham-operated male S100A1 KO mice had higher MAP than female KO mice (122 +/- 5 vs. 93 +/- 3 mmHg, respectively P < 0.05) and reduced survival after MI (4% vs. 27%, respectively, P < 0.05). In isolated aortas and mesenteric arteries, ACh-evoked vasodilatation in KO mice was significantly reduced compared with WT mice (P < 0.05). Nitric oxide production was reduced in endothelial cells isolated from KO mice. Thus, absence of S100A1 results in acute functional impairment and high mortality after MI associated with a gender-specific hypertensive phenotype. S100A1 appears to play a role in the endothelium-dependent regulation of blood pressure.
authors.affiliation: Division of Cardiology, St. Michael's Hospital, University of Toronto, 30 Bond St., Rm. 6-044, Queen Wing, Toronto, ON, Canada M5B 1W8.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Desjardins
authors.forename: Ali
authors.initials: A
authors.lastname: Pourdjabbar
authors.forename: Adrian
authors.initials: A
authors.lastname: Quan
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
authors.forename: Krystyna
authors.initials: K
authors.lastname: Teichert-Kuliszewska
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Parker
mesh_terms: D000777:Anesthetics / Q000009:adverse effects; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D009418:S100 Proteins / Q000172:deficiency* / Q000235:genetics; D012737:Sex Factors; D013997:Time Factors; D014664:Vasodilation; D014991:Xylazine / Q000009:adverse effects
chemical_list: D000777:Anesthetics; D009418:S100 Proteins; C110294:S100A1 protein; D014991:Xylazine; D009569:Nitric Oxide