Potential Cardioprotective Role of Menaquinone-4 Against Cardiac Ischemia-reperfusion Injury

J Cardiovasc Pharmacol. 2023 May 1;81(5):381-388. doi: 10.1097/FJC.0000000000001413.

Abstract

Myocardial infarction is among the leading causes of mortality. Menaquinone-4 (MK-4), a vitamin K2 analog, might play a role in rescuing cardiac ischemia/reperfusion (I/R) injury. This work aimed to discover the potential cardioprotective role of MK-4 against myocardial I/R injury in rats. Thirty-two rats were categorized into 3 groups: (I/R) control group: subjected to I/R protocol (received vehicle), MK-4 preconditioning group: MK-4 infusion for 20 minutes before the I/R protocol, and MK-4 postconditioning group: MK-4 infusion for 20 minutes at the start of the reperfusion phase. The hearts were placed in the Langendorff apparatus, and the left ventricular developed pressure (LVDP), heart rate (HR), + (LV dP/dt) max, - (LV dP/dt) max, and Tau were calculated. The necrotic mass was determined by staining it with nitro blue tetrazolium. Creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C- reactive protein (CRP), as well as cardiac superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) levels were all evaluated. MK-4 postconditioning significantly reduced myocardial infarct size; increased LVDP, + (LV dp/dt) max, - (LV dp/dt) max, and HR; reduced Tau, CK-MB, LDH, CRP, IL-6, TNF-α, MDA, and NOx levels; and increased SOD activity, whereas no significant difference in the GSH level was detected. In conclusion, these data imply that MK-4 may protect the heart from the consequences of I/R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glutathione
  • Interleukin-6 / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardium / pathology
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha* / metabolism
  • Vitamin K 2 / metabolism
  • Vitamin K 2 / pharmacology

Substances

  • menatetrenone
  • Vitamin K 2
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Superoxide Dismutase
  • Glutathione