SHIMIZU Tatsuya    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Professor
Language	English
Title	Functional Evaluation of LYPD1, Novel Angiogenesis Inhibitor Factor, in Rat Heart
Conference	The 83rd Annual Scientific Meeting of the Japanese Circulation Society (JCS2019)
Promoters	Japanese Circulation Society
Conference Type	Nationwide Conferences
Presentation Type	Speech
Lecture Type	General
Publisher and common publisher	◎SAKAMOTO Satoru, HOMMA Jun, AOKI Shinako, SHIMIZU Tatsuya, HAGIWARA Nobuhisa, MATSUURA Katsuhisa
Date	2019/03/29
Venue (city and name of the country)	Yokohama, JAPAN
Summary	*Oral Presentation (English) 7 (CAD) ACS/AMI (Basic) Recently we identified that human cardiac fibroblasts have an angiogenesis inhibitory phenotype through the co-culture experiment with endothelial cells and the responsible factor, LYPD1. LYPD1 expression is localized in the interstitial space in heart and highly expressed in rat heart from embryonic stage and adult. However it remains unclear whether LYPD1 negatively regulate angiogenesis in heart regardless of age and contribute to the pathogenesis in ischemic heart diseases (IHD). Cardiac fibroblasts isolated from neonatal and adult rat heart highly expressed LYPD1 mRNA and inhibited co-cultured endothelial cell network formation in the similar fashion, suggesting that LYPD1 might function to inhibit angiogenesis in the post-natal periods. In coronary permanent ligation model in rats, LYPD1 expression levels were significantly downregulated at day 1 (n=4, p=0.015), but day 8, suggesting that insufficient downregulation of LYPD1 might affect remodeling process of myocardial infarction (MI). Next we generated LYPD1 knock out (k/o) rats using CRISPR/Cas9 system and evaluated the cardiac function after MI throughout blinded and randomized condition. At 4 weeks after MI, the decrease of left ventricular ejection fraction was tended to be attenuated in LYPD1 k/o rats (n=6) compared with wild type rats (n=3) in the limited number of experiments and the enlargement of end diastolic dimension was significantly inhibited in LYPD1 k/o rats (p=0.011). These findings suggest that LYPD1 might have angiogenesis inhibitory function in heart in the post-natal periods and contribute to the remodeling process after MI. Further understanding of mechanisms of LYPD1-mediated angiogenesis inhibition and contribution to myocardial remodeling may lead to develop the newly angiogenic therapy to IHD.