Key result
Kallistatin lowers blood pressure and promotes vasorelaxation while stimulating neointima formation in preclinical models.
Why the study?
Does kallistatin regulate blood pressure and vascular remodeling in preclinical rodent and in vitro vascular models?
Does kallistatin regulate blood pressure and vascular remodeling in preclinical rodent and in vitro vascular models?
Demonstrates that kallistatin regulates blood pressure, vascular smooth muscle proliferation, and angiogenesis independently of the tissue kallikrein-kinin system in preclinical models.
Answers are grounded in this paper and cite their sources.
These rodent effects should not change clinical practice; leaves open kallistatin's role in human hypertension and vascular remodeling.
We have purified, cloned and characterized kallistatin, a tissue kallikrein-binding protein (KBP) in humans and rodents. Kallistatin is a unique serine proteinase inhibitor (serpin) with Phe-Phe residues at the P2 and P1 positions. Structural and functional analysis of kallistatin by site-directed mutagenesis and protein engineering indicate that wild-type kallistatin is selective for tissue kallikrein. Kallistatin is expressed and localized in endothelial and smooth muscle cells of blood vessels and has multiple roles in vascular function independent of the tissue kallikrein-kinin system. First, kallistatin induces vasorelaxation of isolated aortic rings and reduces renal perfusion pressure in isolated rat kidneys. Transgenic mice overexpressing rat kallistatin are hypotensive, and adenovirus-mediated gene delivery of human kallistatin attenuates blood pressure rise in spontaneously hypertensive rats. Second, kallistatin stimulates the proliferation and migration of vascular smooth muscle cells in vitro and neointima formation in balloon-injured rat arteries. Third, kallistatin inhibits the proliferation, migration and adhesion of endothelial cells in vitro and angiogenesis in the rat model of hindlimb ischemia. These results demonstrate novel roles of kallistatin in blood pressure regulation and vascular remodeling.
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Chao et al. (2001) studied Hypertension, arterial injury, and hindlimb ischemia (preclinical rodent and in vitro vascular cell models). Kallistatin (purified protein, transgenic overexpression, or adenovirus-mediated gene delivery) was evaluated on Blood pressure regulation, vasorelaxation, vascular smooth muscle cell proliferation/neointima formation, and endothelial cell angiogenesis. Kallistatin induces vasorelaxation, lowers blood pressure in rodent models, stimulates smooth muscle proliferation and neointima formation, and inhibits endothelial angiogenesis.
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