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Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases

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Abstract

Cardiovascular diseases (CVDs) are the world’s leading cause of death, accounting for 32% of all fatalities. Although therapeutic agents are available for CVDs, however, most of them have significant limitations such as the time-dependency effect, hypotension, and bradycardia. To overcome the limitations of current pharmacological therapies, new molecular targets and pathways need to be identified and investigated to provide better treatment options for CVDs. Recent evidence suggested the involvement of pyruvate kinase M2 (PKM2) and targeting PKM2 by its modulators (inhibitors and activators) has shown promising results in several CVDs. PKM2 regulates gene activation in the context of apoptosis, mitosis, hypoxia, inflammation, and metabolic reprogramming. PKM2 modulators might have a significant impact on the molecular pathways involved in CVD pathogenesis. Therefore, PKM2 modulators can be one of the therapeutic options for CVDs. This review provides an insight into PKM2 involvement in various CVDs along with their therapeutic potential.

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Abbreviations

ADP:

Adenosine diphosphate

Akt:

Serine/threonine protein kinase

ATP:

Adenosine triphosphate

AMPK:

5′ Adenosine monophosphate-activated protein kinase

Bcl2:

B cell lymphoma 2

CK-MB:

Creatine kinase-MB

COX-2:

Cyclooxygenase-2

DMAMCL:

Dimethylaminomicheliolide

DASA-58:

3-(4-(2,3-Dihydrobenzo[b] [1, 4] dioxin-6-ylsulfonyl)-1,4-diazepan-1-ylsulfonyl) aniline

FGF:

Fibroblast growth factor

GLUT-1:

Glucose transporter 1

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

GSK3:

Glycogen synthase kinase 3

HK-2:

Hexokinase 2

HSP90:

Heat shock protein 90

IL-1β:

Interleukin 1 beta

iNOS:

Inducible nitric oxide synthase

Jak2:

Janus kinase 2

MDA:

Malondialdehyde

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinases

mTOR:

Mammalian target of rapamycin

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-kB:

Nuclear factor kappa B

NLRP3:

NLR family pyrin domain-containing 3

Oct4:

Octamer-binding transcription factor 4

Ox-LDL:

Oxidized low-density lipoprotein

p53:

Tumor suppressor p53

PDK-2:

Pyruvate dehydrogenase kinase isoform 2

RAC1:

Rac family small GTPase 1

ROS:

Reactive oxygen species

Smad2/3:

Signal transducer protein for TGF-β

SAICAR:

Succinylaminoimidazolecarboxamide ribose-5′-phosphate

SOD:

Superoxide dismutase

Src:

Non-receptor tyrosine kinase

STAT3:

Signal transducer and activator of transcription 3

TGF-β:

Transforming growth factor beta

TEPP-46:

6-[(3 Aminophenyl) methyl]-4,6-dihydro-4-methyl-2-(methylsulfinyl)-5 h-thieno [2′,3′:4,5] pyrrolo [2,3-d] pyridazin-5-one

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Acknowledgements

We would like to acknowledge Sakeel, Nishit, and Ashish for assisting/reading for improvement.

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Support was provided by the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India to NIPER SAS Nagar.

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  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India

    Mohd Rihan & Shyam Sunder Sharma

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M. R. and S. S. S. conceived the idea of the manuscript. M. R. wrote all the sections. S. S. S. corrected the manuscript and all authors approved the final proof for submission.

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Rihan, M., Sharma, S.S. Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases. J. of Cardiovasc. Trans. Res. 16, 382–402 (2023). https://doi.org/10.1007/s12265-022-10321-1

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