title: Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice.
abstract: Lysyl oxidase (LOX) and LOX-like protein-1 (LOXL-1) are extracellular matrix-embedded amine oxidases that have critical roles in the cross-linking of collagen and elastin. LOX family proteins are abundantly expressed in the remodeled heart of animals and humans and are implicated in cardiac fibrosis; however, their role in cardiac hypertrophy is unknown. In this study, in vitro stimulation with hypertrophic agonists significantly increased LOXL-1 expression, LOX enzyme activity and [(3)H] leucine incorporation in neonatal rat cardiomyocytes. A LOX inhibitor, beta-aminopropionitrile (BAPN), inhibited agonist-induced leucine incorporation in cardiomyocytes in vitro, suggesting the involvement of LOXL-1 in cardiomyocyte hypertrophy. Abdominal aortic constriction in rats produced left ventricular hypertrophy in parallel with LOXL-1 mRNA upregulation. And BAPN administration significantly inhibited angiotensin II-induced cardiac hypertrophy in vivo. These results suggest a role of LOXL-1 in cardiac hypertrophy in vivo. We generated transgenic mice with cardiomyocyte-specific expression of LOXL-1. LOXL-1 transgenic mice pups were born normally and grew to adulthood without increased mortality; these mice exhibited a greater left ventricle to body weight ratio, larger myocyte diameter, and more brain natriuretic peptide expression than their wild-type littermates. Echocardiography revealed that the LOXL-1 transgenic mice also had greater wall thickness with preserved cardiac contraction. Our results indicate a possible fundamental role of LOXL-1 in cardiac hypertrophy.
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Haruya
authors: H
authors: Ohmura
authors: Hideo
authors: H
authors: Yasukawa
authors: Tomoko
authors: T
authors: Minami
authors: Yusuke
authors: Y
authors: Sugi
authors: Toyoharu
authors: T
authors: Oba
authors: Takanobu
authors: T
authors: Nagata
authors: Sachiko
authors: S
authors: Kyogoku
authors: Hideki
authors: H
authors: Ohshima
authors: Hiroki
authors: H
authors: Aoki
authors: Tsutomu
authors: T
authors: Imaizumi
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D000629:Aminopropionitrile / Q000494:pharmacology; D000804:Angiotensin II / Q000009:adverse effects / Q000187:drug effects / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D000804:Angiotensin II; D000629:Aminopropionitrile; D000594:Amino Acid Oxidoreductases; C574516:LOXL1 protein, rat; C482019:Loxl1 protein, mouse; D007930:Leucine