Grant: Travel Awards - Institute Community Support

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis and is characterized by an accumulation of plaque within the arteries supplying blood to the lower extremities. In result, the lower limbs lack a sufficient amount of blood (ischemia) to maintain adequate muscle health. When the skeletal muscle lacks oxygen and nutrients, it becomes damaged and non-functional, which leads to negative disease outcomes such as exercise intolerance, pain and muscle tissue death. PAD is strongly associated with other co-morbidities such as insulin resistance and diabetes (often outcomes of high fat (HF) diet-induced obesity) that worsen the healing response to skeletal muscle ischemia. HF diet and obesity are shown to cause low-grade systemic inflammation and microvascular adaptations that may impact ischemia outcomes. Our goal of the study is to identify how HF diet alters the healing of ischemic muscle. We hypothesized that HF diet would impair the regenerative capacity of ischemic muscle. Male mice were fed a HF or normal chow (NC) diet (9 weeks). Small blood vessel (capillary) blood flow was assessed in one group of mice. The capillaries of HF mice exhibited higher red-blood-cell flow speed and oxygen delivery compared to NC mice. HF and NC mice were subjected to lower leg ischemia and muscle healing was analyzed. Surprisingly, ischemic muscle from HF fed mice exhibited multiple signs of improved recovery, including blood vessel growth, blood flow recovery and signs of muscle regeneration. Our data suggest that moderate duration HF diet promotes a more favourable microenvironment that potentially improves the healing of ischemic muscle. Due to the increasing prevalence of vascular disease in Canada, our results provide a valuable insight into understanding the role of HF diet-induced obesity on PAD outcomes. From a clinical perspective, this knowledge can potentially be utilized into improving the well-being of patients suffering from PAD.