Fight Aging!

Researchers here show that activated protein C (APC) is involved in the mechanisms that cause cell death and dysfunction subsequent to ischemia, the temporary loss of flow of blood to tissue, and reperfusion, the return of that supply. Much of the harm following a heart attack or stroke might be avoided if cells just behaved differently. Researchers found that APC activity is reduced in old tissues, and this makes cells more vulnerable. Upregulation of APC may help to somewhat reduce the consequences of ischemia.

APC, a protein circulating in blood, has both anticoagulant (blood clot prevention) and anti-inflammatory functions that can help protect cells from disease and injury. Endothelial protein C receptor (EPCR) - located both on cells lining blood vessels and on the surface of cell membranes, including heart muscle cells - is associated with increased APC production and regulates APC's subsequent cell signaling (or cell communication).

The stress of ischemia and reperfusion injury induced "shedding" of EPCRs in young and old wild-type mice - that is, a greater number of these receptors were cut from the heart muscle cell membrane and then moved into the bloodstream. This EPCR shortage (deficiency) in the heart can impair activated protein C signaling critical for favorably regulating energy metabolism and anti-inflammatory responses, preventing cell death, and stimulating other activities needed to protect cardiac muscle cells. While the hearts of the old and young wild-type mice both showed EPCR shedding, older hearts experienced a more severe EPCR deficiency and decline in APC signaling activity in response to reperfusion injury.

Administering APC or its derivatives helped reduce heart damage inflicted by ischemia and reperfusion, particularly in the old mice. Digging deeper, the researchers discovered that by stabilizing (maintaining) EPCR on the cardiac cell membrane, APC strengthens the aging heart's resistance both to heart attack-related ischemia and to injury associated with restoring coronary artery blood flow.

The researchers detailed how APC treatments improve cardiac function by regulating both acute (short-term) and chronic (longer-term) metabolic pathways. They demonstrated that enzyme AMPK (AMP-activated protein kinase) mediates an acute adaptive response to cardiac stress immediately following heart attack, while enzyme AKT (protein kinase B) regulates chronic metabolic adjustments to reperfusion stress over time. APC treatment led to better enzyme activity and more efficient energy balance needed to contract cardiac muscle cells and pump blood from the heart to the rest of the body.

Link: https://hscweb3.hsc.usf.edu/blog/2022/01/27/activated-protein-c-can-protect-against-age-related-cardiac-ischemia-and-reperfusion-injury-preclinical-study-finds/