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Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation.
Cardiovasc Res. 2007 Jan 01; 73(1):130-42.CR

Abstract

OBJECTIVE

We assessed the role of glycogen synthase kinase-3beta (GSK-3beta) and kinin B2 receptor in mediating tissue kallikrein's protective effects against cardiac hypertrophy.

METHODS

We investigated the effect and mechanisms of tissue kallikrein using hypertrophic animal models of rats as well as mice deficient in kinin B1 or B2 receptor after aortic constriction (AC).

RESULTS

Intramyocardial delivery of adenovirus containing the human tissue kallikrein gene resulted in expression of recombinant kallikrein in rat myocardium. Kallikrein gene delivery improved cardiac function and reduced heart weight/body weight ratio and cardiomyocyte size without affecting mean arterial pressure 28 days after AC. Icatibant and adenovirus carrying a catalytically inactive GSK-3beta mutant (Ad.GSK-3beta-KM) abolished kallikrein's effects. Kallikrein treatment increased cardiac nitric oxide (NO) levels and reduced NAD(P)H oxidase activity and superoxide production. Furthermore, kallikrein reduced the phosphorylation of apoptosis signal-regulating kinase1, mitogen-activated protein kinases (MAPKs), Akt, GSK-3beta, and cAMP-response element binding (CREB) protein, and decreased nuclear factor-kappaB (NF-kappaB) activation in the myocardium. Ad.GSK-3beta-KM abrogated kallikrein's actions on GSK-3beta and CREB phosphorylation and NF-kappaB activation, whereas icatibant blocked all kallikrein's effects. The protective role of kinin B2 receptor in cardiac hypertrophy was further confirmed in kinin receptor knockout mice as heart weight/body weight ratio and cardiomyocyte size increased significantly in kinin B2 receptor knockout mice after AC compared to wild type and B1 receptor knockout mice.

CONCLUSIONS

These findings indicate that tissue kallikrein, through kinin B2 receptor and GSK-3beta signaling, protects against pressure overload-induced cardiomyocyte hypertrophy by increased NO formation and oxidative stress-induced Akt-GSK-3beta-mediated signaling events, MAPK and NF-kappaB activation.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17137568

Citation

Li, Huey-Jiun, et al. "Tissue Kallikrein Protects Against Pressure Overload-induced Cardiac Hypertrophy Through Kinin B2 Receptor and Glycogen Synthase Kinase-3beta Activation." Cardiovascular Research, vol. 73, no. 1, 2007, pp. 130-42.
Li HJ, Yin H, Yao YY, et al. Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation. Cardiovasc Res. 2007;73(1):130-42.
Li, H. J., Yin, H., Yao, Y. Y., Shen, B., Bader, M., Chao, L., & Chao, J. (2007). Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation. Cardiovascular Research, 73(1), 130-42.
Li HJ, et al. Tissue Kallikrein Protects Against Pressure Overload-induced Cardiac Hypertrophy Through Kinin B2 Receptor and Glycogen Synthase Kinase-3beta Activation. Cardiovasc Res. 2007 Jan 1;73(1):130-42. PubMed PMID: 17137568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation. AU - Li,Huey-Jiun, AU - Yin,Hang, AU - Yao,Yu-Yu, AU - Shen,Bo, AU - Bader,Michael, AU - Chao,Lee, AU - Chao,Julie, Y1 - 2006/10/27/ PY - 2006/05/02/received PY - 2006/10/17/revised PY - 2006/10/18/accepted PY - 2006/12/2/pubmed PY - 2007/4/11/medline PY - 2006/12/2/entrez SP - 130 EP - 42 JF - Cardiovascular research JO - Cardiovasc. Res. VL - 73 IS - 1 N2 - OBJECTIVE: We assessed the role of glycogen synthase kinase-3beta (GSK-3beta) and kinin B2 receptor in mediating tissue kallikrein's protective effects against cardiac hypertrophy. METHODS: We investigated the effect and mechanisms of tissue kallikrein using hypertrophic animal models of rats as well as mice deficient in kinin B1 or B2 receptor after aortic constriction (AC). RESULTS: Intramyocardial delivery of adenovirus containing the human tissue kallikrein gene resulted in expression of recombinant kallikrein in rat myocardium. Kallikrein gene delivery improved cardiac function and reduced heart weight/body weight ratio and cardiomyocyte size without affecting mean arterial pressure 28 days after AC. Icatibant and adenovirus carrying a catalytically inactive GSK-3beta mutant (Ad.GSK-3beta-KM) abolished kallikrein's effects. Kallikrein treatment increased cardiac nitric oxide (NO) levels and reduced NAD(P)H oxidase activity and superoxide production. Furthermore, kallikrein reduced the phosphorylation of apoptosis signal-regulating kinase1, mitogen-activated protein kinases (MAPKs), Akt, GSK-3beta, and cAMP-response element binding (CREB) protein, and decreased nuclear factor-kappaB (NF-kappaB) activation in the myocardium. Ad.GSK-3beta-KM abrogated kallikrein's actions on GSK-3beta and CREB phosphorylation and NF-kappaB activation, whereas icatibant blocked all kallikrein's effects. The protective role of kinin B2 receptor in cardiac hypertrophy was further confirmed in kinin receptor knockout mice as heart weight/body weight ratio and cardiomyocyte size increased significantly in kinin B2 receptor knockout mice after AC compared to wild type and B1 receptor knockout mice. CONCLUSIONS: These findings indicate that tissue kallikrein, through kinin B2 receptor and GSK-3beta signaling, protects against pressure overload-induced cardiomyocyte hypertrophy by increased NO formation and oxidative stress-induced Akt-GSK-3beta-mediated signaling events, MAPK and NF-kappaB activation. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/17137568/Tissue_kallikrein_protects_against_pressure_overload_induced_cardiac_hypertrophy_through_kinin_B2_receptor_and_glycogen_synthase_kinase_3beta_activation_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2006.10.014 DB - PRIME DP - Unbound Medicine ER -