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Review
. 2022 Jun 23;11(13):3638.
doi: 10.3390/jcm11133638.

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

Silvia Ortona  1 , Chiara Barisione  2 , Pier Francesco Ferrari  3 , Domenico Palombo  1   2   4 , Giovanni Pratesi  1   2
Affiliations
Review

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

Silvia Ortona et al. J Clin Med. .

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.

Keywords: PCSK9; PPARs; acute kidney injury (AKI); acute myocardial infarction (AMI); adipokines; ischemia/reperfusion injury; ischemic stroke; myostatin (MSTN); vascular surgery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 2
Figure 2
Biochemical events triggering ischemia/reperfusion injury (adapted with permission from Ref. [13] 2022, Piccin Editore).
Figure 1
Figure 1
Pathological processes associated with ischemia/reperfusion in cells and tissues.
Figure 3
Figure 3
Acute myocardial infarction and heart/brain/kidney axis. (A): Ischemic stroke after AMI, driven by increased fibrinogen levels, thromboembolism from left ventricle, and sympathetic activation; (B): Kidney injury after AMI, driven by increased ROS and renal tubular damage, hypoperfusion, and systemic inflammation; (C): Heart disease in CKD: increased inflammation, ROS production, accumulation of vasoactive uremic toxins, and ER stress.
Figure 4
Figure 4
Surgically-induced ischemia during abdominal aortic aneurysm repair.
Figure 5
Figure 5
Mechanism for protection of anti-PCSK9.
See this image and copyright information in PMC

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