PCSK9 and Other Metabolic Targets to Counteract Ischemia/Reperfusion Injury in Acute Myocardial Infarction and Visceral Vascular Surgery

Abstract

Ischemia/reperfusion (I/R) injury complicates both unpredictable events (myocardial infarction and stroke) as well as surgically-induced ones when transient clampage of major vessels is needed. Although the main cause of damage is attributed to mitochondrial dysfunction and oxidative stress, the use of antioxidant compounds for protection gave poor results when challenged in clinics. More recently, there is an assumption that, in humans, profound metabolic changes may prevail in driving I/R injury. In the present work, we narrowed the field of search to I/R injury in the heart/brain/kidney axis in acute myocardial infarction, major vascular surgery, and to the current practice of protection in both settings; then, to help the definition of novel strategies to be translated clinically, the most promising metabolic targets with their modulatory compounds—when available—and new preclinical strategies against I/R injury are described. The consideration arisen from the broad range of studies we have reviewed will help to define novel therapeutic approaches to ensure mitochondrial protection, when I/R events are predictable, and to cope with I/R injury, when it occurs unexpectedly.

Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

“…Additionally, donor-specific antibodies do not increase after 1 month of treatment ( 162 ). PCSK9 is a potential marker of ischemia/reperfusion injury during visceral vascular surgery or myocardial infarction ( 163 ). Ischemia/reperfusion triggers the upregulation of PCSK9 and increased the levels of autophagy regulatory proteins light chain 3 and beclin-1, at the same time, activating the Bcl-2/adenovirus E1B 19-kDa interacting protein pathway aggravated ischemia/reperfusion injury ( 164 ).…”

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases

“…Meanwhile, multiple studies have reported that myostatin levels increase in the hearts and blood of mice 12 h after MI and 10 min after ischemia. Myostatin was also induced in rat kidney ischemia and reperfusion conditions and was correlated with mitochondrial damage [ 14 ]. These studies thus suggest that myostatin is involved in MI-related cachexia development, and its expression seems upregulated during MI, indicating its potential as a valuable clinical marker.…”

Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis

“…For example, inhibition of PCSK9 was demonstrated to reduced myocardial ischemia-/reperfusion injury via BNIP-3 mediated autophagic pathway and improved myocardial infarct size and subsequent cardiac function. By investigating the functional role of PCSK9 inhibitions in the metabolic targets, it could potentially lead to better understanding of the pathogenesis of myocardial infarction and ischemic stroke, as well as provide a potential therapeutic target for its management ( 11 ). Additionally, the knowledge gained from exploring the role of PCSK9 in cell proliferation and apoptosis could help to elucidate the potential involvement of this protein in cancer risk, providing insight into potential preventive strategies ( 12 ).…”