Review of the Protective Mechanism of Curcumin on Cardiovascular Disease

Abstract

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.

Keywords:

• curcumin
• intima
• endothelial cells
• vascular smooth muscle cell
• cardiovascular diseases
• inflammation
• apoptosis

Abbreviations

CVDs, Cardiovascular diseases; DCM, Diabetic cardiomyopathy; VSMCs, Vascular smooth muscle cells; VECs, vascular endothelial cells; ROS, Reactive oxygen species; Nrf2, Nuclear factor erythroid factor 2 related factor 2; Keap1, Kelch-like ECH-associated protein 1; ARE, antioxidant response element; HO-1, Heme oxygenase-1; H₂O_2, Hydrogen peroxide; HUVECs, Human umbilical vein endothelial cells; AS, atherosclerosis; SHRs, Spontaneously hypertensive rats; UCP2, uncoupling protein-2; NO, nitric oxide; 2K-1C, 2kidney-1clip; MMPs, matrix metalloproteinases; NADPH, nicotinamide adenine dinucleotide phosphate; PKC, protein kinase C; CD40, cluster of differentiation 40; CD40L, cluster of differentiation 40 ligand; TLR, Toll-like receptor; NF-κB, Nuclear factor kappa-B; HFD, high-fat diet; VCAM-1, Vascular cell adhesion molecule-1; ICAM-1, Intercellular cell adhesion molecule-1; TNF-α, Tumor necrosis factor α; HMGB1, High mobility group box protein 1; HECs, human endothelial cells; LPS, Lipopolysaccharide; HCMV, human cytomegalovirus; ox-LDL, moxidized low-density lipoprotein; MyD88, Myeloid differentiation factor 88; LCN2, Lipocalin-2; p38 MAPK, p38 mitogen-activated protein kinase; HAECs, Human arterial endothelial cells; TAECs, Thoracic aortic endothelial cells; PI3K, phosphatidyinositol 3-kinase; Akt, protein kinase B; AGEs, Advanced glycation end products; MGO, Methylglyoxal; HDL, high-density lipoprotein; ERS, endoplasmic reticulum stress; IL-8, interleukin-8; COX-2, Cyclooxygenase; CREB, cyclic adenosine monophosphate(cAMP)-response element binding protein; PLLA, poly-L-lactic acid; MCP-1, Monocyte chemoattractant protein 1; RAECs, Rat aortic endothelial cells; LOX-1, lectin-like ox-LDL receptor-1; TC, total cholesterol; TG, Total triglycerides; LDL-C, low-density lipoprotein cholesterol; Apo B, Apolipoprotein B; GSH, glutathione; GSH-Px, glutathione peroxidase; SR-A, Scavenger receptor class A; CD36, differentiation 36; SR-BI, Class B scavenging receptor type I; ABCA1, ATP-binding cassette transporters A1; ABCG1, ATP-binding cassette transporters G1; Sirt 6, Silent information regulator 6; LXRs, Liver X receptors; JNK, c-Jun N-terminal kinase; AMPK, AMP-activated protein kinase; FAT, fatty acid translocase; FABP4, Fatty acid binding protein 4; HIF-1α, Hypoxia inducible factor-1α; ERK, extracellular regulated protein kinase; PPAR γ, Proliferator-activated receptor γ; TMAO, trimethylamine-N-oxide; EMMPRIN, Extracellular matrix metalloproteinase inducer; PMA, Phorpol 12 myristic acid 13 acetate; THBS, Thrombospondins; DM, Diabetes mellitus; EPCs, Endothelial progenitor cells; EPCD, Endothelial progenitor cell dysfunction; MnSOD, Manganese superoxide dismutase; VEGF, Vascular endothelial cell growth factor; Ang-1, Angiotensin 1; PAD, Peripheral arterial disease; FAK, focal adhesion kinase; CsA, Cyclosporine A; eNOS, endothelial nitric oxide synthase; HMEC, Human microvascular endothelial cells; IRS-1, insulin receptor substrate 1; mTOR, mammalian target of rapamycin; BECN1, beclin1; TFEB, transcription factor EB; BRD4, bromodomain-containing protein 4; NLRP3, NOD- LRR- and pyrin domain-containing protein 3; EndMT, Endothelial-to-mesenchymal transition; TGF-β1, Transforming growth factor-β1; Nrf-2, nuclear factor erythroid-2-related factor 2; DDAH, dimethylarginine dimethylaminohydrolase; ADMA, asymmetric dimethylarginine; TRPV4, Transient receptor potential vanilloid 4; Ang II, Angiotensin II; SP1, specific protein 1; CMKLR1, chemokine-like receptor 1; IGF-1, Insulin-like growth factor 1; PKB, protein kinase B; GSK-3β, glycogen synthase kinase-3β; Egr-1, early growth response protein 1; Ras, rat sarcoma; MEK1/2, mitogen-activated protein kinase kinase 1/2; CRP, C-reactive protein; RAAS, renin aniotension aldosterone system; AT1R, angiotensin type 1 receptor; ET-1, Endothelin-1; IGF-1R, IGF-1 receptor; PTEN, phosphatase and tensin homolog; FMD, Flow-mediated dilation; I/R, Ischemia and reperfusion; JAK, Janus kinase; STAT, Signal transducer and activator of transcription; SD, Sprague Dawley; H/R, Hypoxia/reoxygenation; ISO, Isoproterenol; mPTP, mitochondrial permeability transition pore; Hsps, Heat shock proteins; CME, Coronary microembolism; HAT, Histone acetyltransferase; GATA4, GATA binding protein 4; DS, Dahl salt-sensitive; NCX, Na⁺/Ca²⁺ exchanger; TAC, Transverse aortic constriction; NFAT, nuclear factor of activated T cells; ECM, Extracellular matrix; CFs, Cardiac fibroblasts; Smad, mothers against decapentaplegic homolog; α-SMA, α-smooth muscle actin; CTGF, connective tissue growth factor; FN, fibronectin; TIMPs, tissue inhibitor of matrix metalloproteinases; AT2R, type 2 receptor; MI, myocardial infarction; PAH, Pulmonary arterial hypertension; RV, Right ventricular; DKK-3, Dickkopf related protein 3; AM, Autoimmune myocarditis; iNOS, inducible nitric oxide synthase; FOXO1, forkhead box protein O1; EAM, Experimental AM; CaMKII, Calmodulin-dependent protein kinase II; DOX, Doxorubicin; Rac 1, ras related C3 botulinum toxin substrate 1; TWEAK, tumor necrosis factor-like weak inducer of apoptosis; Fn14, fibroblast growth factor-inducible protein 14; CAT, Catalase; MDA, Malondialdehyde; CP, Cyclophosphamide; CPT-11, Irinotecan; BEV, Bevacizumab; ABE, Abemacilib; CK-MB, creatine kinase-MB; cTnI, cardiac troponin I; TSP, thrombospondin; VEGFR, VEGF receptor; NEC, nano-emulsion curcumin; SERCA2a, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a.

Credit Authorship Contribution Statement

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Data Sharing Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This study was funded by grants from General Program of National Natural Science Foundation of China (Grant no. 81973836), Science and Technology Innovation Project of China Academy of Chinese Medical Sciences (Grant no. CI2021A00902).