The Role of Caspase-1 Activation in Ischemic Muscle: Implications for Treatment of PAD and COVID-19

Presenter: Dr. Ulka Sachdev-Ost, Department of Surgery

Dr. Sachdev's research focuses on peripheral artery disease and the modelcular mechanisms leading to muscle ischemia and damage because of defects in peripheral blood supply. 

The pandemic caused by the novel coronavirus 2019-nCoV has infected millions of individuals and killed close to 200,000 people in the United States. Individuals >65yr who are most at risk for complications from the current coronavirus disease (COVID-19), are also prone to cardiovascular issues like peripheral arterial disease (PAD). Therapeutics must therefore account for confounding comorbidities that might complicate treatment. The current coronavirus may cause inflammation similar to that associated with severe acute respiratory syndrome (SARS). It has been shown that SARS-related peptides aggregate in cells, activate inflammasomes and inflammatory cell death (pyroptosis) through caspase-1 activation. This promotes the release of cytokines and DAMPS from inflammatory cells and allows for cellular debris to deposit in lung tissue. In this talk, Dr. Sachdev will describe ways in which we have shown caspase-1 to be activated in ischemic muscle, both in animal models and in patients. She will also discuss current ways in which purported therapies like hydroxychloroquine might cause inadvertent effects in ischemic muscle, causing side effects in those patients most at risk for both COVID-19 and PAD.

Articles that may provide some good background on caspase-1 in muscle ischemia: 

• Cardiovascular Complications Associated with COVID-19 and Potential Therapeutic Strategies
• Caspase1/11 signaling affects muscle regeneration and recovery following ischemia, and can be modulated by chloroquine