Decreased cardiac function and increased cardiac lymphangiogenesis in CR6 interacting factor 1 knock-out mice

Purpose: Because CR6-interacting factor (CRIF1) contacting colied-coil domain is required for both genomic stability and mitochondrial integrity, CRIF1 deficiency might be associated with impaired cardiac function. Cardiac lymphatic system plays important roles in myocardial fluid homeostasis, controlling inflammation and infection. Because this system can participate in the various stages of myocardial infarction and inflammation, the study of this lymphatic system can elucidate the pathologic process of many cardiovascular diseases. So, We performed this study to determine the role of CRIF1 on cardiac function and lymphangiogenesis in a CRIF1 knock-out mice hearts. Methods and results: CRIF1-deficient mouse was embryonic lethal, we made heart specific -knock-out mice. Cre-alpha MHC transgenic mice were bred with mice containing loxP-CRIF1. Knock-out was confirmed by RT-PCR. Serial echocardiography showed slightly decreased left ventricular ejection fraction and fractional shortening in the CRIF1 knock-out (+/-) mice compared to wild type mice. Electromicroscopy revealed that the mitochondria of CRIF1 knock-out (+/-) cardiomyocytes showed abnormal morphogenesis. The cells showed excessively fragmented mitochondria, intracriatal swelling and thinning of myocardial fiber. The stability of mitochondrial complexes in CRIF1-deficient cells showed marked derangements. Lymphatic vessels were much developed in the CRIF1 knock-out (+/-) mice compared to wild type mice. Lymphangiogenetic factors such as Lyve-1 were expressed at significantly higher levels in the CRIF1 deficient mice hearts ((p<0.05). Conclusions: Cardiac systolic function was impaired and Lymphatic vessels were much developed in the CRIF1 knock-out (+/-) mice. Therefore, CRIF1 is required for maintenance of normal cardiac function and lymphangiogenesis has an important role in the pathogenesis of heart failure due to CRIF 1 deficiency.