Functional effect of cardiovascular kidney metabolic syndrome on peripheral arterial disease
Embargo Date
2028-02-09
OA Version
Citation
Abstract
Cardiovascular kidney metabolic syndrome (CKM) affects roughly 90% of people in the USA. It profoundly increases the risk of cardiovascular disease and PAD. To this date, no reliable animal models of CKM investigate the renal and cardiometabolic impact on peripheral artery disease. So, we developed an animal model to investigate CKM using PAD. Four groups of C57BL/6 mice were randomized. Normal diet (ND), adenine diet (AD, a CKD model), high-fat diet (HFD, a metabolic model), and a combination of HFD+AD (a potential CKM model). Mice underwent a hind limb ischemia surgery, a femoral artery ligation, and subsequent exercise treadmill testing. Compared to ND mice, the AD and HFD+AD mice showed similar reductions in the hind limb perfusion ratios, time to exhaustion, and distance traveled. Compared to ND mice, all the other groups showed a reduction in angiogenesis, as shown by CD31, and an increase in immune infiltration, as reflected by CD45+ cells within the ischemic limb. HFD+AD mice displayed profound alterations in perfusion, post-ischemic angiogenesis, infiltration of immune cells in the ischemic muscle, a decreased perfusion ratio, an altered flux ratio, decreased exhaustion time and distance traveled, and grip strength. This functionally characterized CKM model for PAD can be explored further to probe the mechanism.
Description
2025