Mwf rat as a novel animal model of cardiorenal syndrome type iv

Objective: Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to cardiac dysfunction and an increase in cardiovascular events. There is an unmet need for suitable animal models of CRS to further define the pathogenesis and progression of CRS to test new therapeutic strategies. We aim to determine if CKD in aged Munich Wistar Frömter (MWF) rat may translate to cardiovascular alterations of CRS. Design and method: Profibrotic markers and angiotensin receptor (ATR) expression was measured by RT-q-PCR in kidney, aorta and heart from 22 and 45-week-old (aged) male MWF rats (n = 7-10/group). Results: Aged MWF showed higher renal expression of tubular damage markers (Kim-1 and Ngal) and profibrotic factors (Col1A1, Col3A1, TGF-beta) together with lower levels of AT2R. Thoracic aorta also exhibited increased expression of profibrotic CTGF-1 and Col1-A1, as well as a lower AT2R expression. Both age groups were hypertensive with similar systolic and diastolic blood pressure levels. However, aged MWF had an increased PWV and heart weight, together with increased intrinsic arterial stiffness and an outward hypertrophic remodeling in mesenteric arteries. In 45-week-old MWF, levels of cardiac CTGF-1, AT1R and AT2R were higher, whereas TGF-beta expression was lower. No differences were observed for Col1A1 or Col3A1. Conclusions: The presence of renal and vascular fibrosis, hypertension, arterial stiffness and cardiac hypertrophy, together with inflammation, vascular remodeling and early profibrotic cardiac environment, potentially counterregulated by AT2R make aged-MWF rat an useful model for CRS study.