Open Access Austin Journal of Cardiovascular Disease and Atherosclerosis Review Article Cardioprotection by Bioactive Polyphenols: A Strategic View Chu AJ* Department of Surgery, School of Medicine, Wayne State Abstract University, Detroit, USA Cardiovascular disease (CVD) remains one causing most mortality *Corresponding author: Arthur J. Chu, Department worldwide. Common CVD risks include oxidative stress, hyperlipidemia, of Surgery, School of Medicine, Wayne State University, endothelial dysfunction, thrombosis, hypertension, hyperhomocysteinemia, Detroit, USA inflammation, diabetes, obesity, physical inactivity, and genetic factors. Among which, lifestyle changes including diets are modifiable CVD risks, becoming Received: February 15, 2018; Accepted: March 23, the first line of prevention prior to any medication. In the past decades, the 2018; Published: March 30, 2018 USDA, the American Heart Association, the American Nutrition Association, the Academy of Nutrition and Dietetics, and many other health organizations have launched five colors daily with vegetable and fruit consumption for human health. Lipophilic polyphenols, phytochemicals rich in vegetables and fruits, show classical antioxidation (e.g., radical-scavenging, metal chelating, NOX inhibition, attenuation on mitochondrial respiration, inhibition on xanthine oxidase, and upregulations on endogenous antioxidant enzymes), multiple effects on cell signaling (e.g., AMPK activation, SirT1 activation, eNOS activation, FOXO activation, NFkB inactivation, PI3K/AkT inhibition, mTORC1 inhibition, ERK inhibition, JAK/STAT inhibition, IKK/JNK inhibition, PDE inhibition, α-catenin inactivation, downregulation on TLR expression, ACE inhibition, adiponectin elevation, attenuated ET-1 production, and K+ channel activation), and many other biological actions (e.g., inhibition on α-glucosidase, anticoagulation, upregulation on paraoxonase 1, PAI-1 downregulation, tPA upregulation, epigenetic modulation, and altered gut microbiota). Accordingly, polyphenols multiple-targeting CVD risks and progression (Graphic summary) could offer broad range of cardioprotection from atherosclerosis, hypertrophy, arrhythmia, angina, heart failure, etc. Keywords: Polyphenol; Anti-Oxidation; Cardiovascular Disease; Hyperlipidemia; Inflammation; Diabetes; Obesity; Cell Signaling; AMPK; Mtorc1; PI3K; FOXO Graphical Abstract: Austin J Cardiovasc Dis Atherosclerosis - Volume 5 Issue 1 - 2018 Citation: Chu AJ. Cardioprotection by Bioactive Polyphenols: A Strategic View. Austin J Cardiovasc Dis ISSN: 2472-3568 | www.austinpublishinggroup.com Atherosclerosis. 2018; 5(1): 1034. Chu. © All rights are reserved Chu AJ Austin Publishing Group Abbreviations Element Binding Protein; STAT: Signal Transducer and Activator of Transcription; SVEP1: Sushi, Von Willebrand Factor Type A, EGF ACC: Acetyl-CoA Carboxylase; ACE: Angiotensin Converting and Pentraxin Domain Containing 1; TAFI: Thrombin Activatable Enzyme; AF: Atrial Fibrillation; AGE: Advanced Glycation End- Fibrinolysis Inhibitor; TF: Tissue Factor ; TFPI: TF Pathway Inhibitor; Product; Akt: Protein Kinase B; AMPK: AMP-Activated Protein TG: Triglyceride ; TLR: Toll-Like Receptor ; TMA: Trimethylamine; Kinase; ANGPTL: Angiopoietin-Like; AP-1: Activated Protein-1; tPA: Tissue Plasminogen Activator; Treg: Regulatory T Cells; APC: Activated Protein C; Apo: Apolipoprotein; aPTT: Activated TSC: Tuberous Sclerosis Complex; TT: Thrombin Time; TxA2: Partial Thrombin Time; AT III: Antithrombin; AT: Angiotensin; Thromboxane A2; UCP1: Uncoupling Protein 1; VLDL: Very Low AXL: Receptor Tyrosine Kinase AXL (Anexelekto; Uncontrolled); Density Lipoprotein; VSMC: Vascular Smooth Muscle Cell; vWF: BAS: Bile Acid Sequestrants; BP: Blood Pressure; C/REBP: cAMP Von Willebrand Factor Response Element-Binding Protein; cAMP: Cyclic Adenosine Monophosphate; cGMP: Cyclic Guanosine Monophosphate; CM: Introduction Chylomicron; COX: Cyclooxygenase; CRP: C-Reactive Protein; In retrospect, the twentieth century marked cardiovascular CVD: Cardiovascular Disease; DHA: Docosahexaenoic Acid; DPP- disease (CVD) as the most common mortality in US, which reached 4: Dipeptidyl Peptidase 4; EC: Endothelial Cell; ECM: Extracellular a peak-high death rate of nearly 350 deaths per 100,000 populations Matrix; EGC: Epigallocatechin; EGCG: EGC Gallates; EPA: around 1950s to 1970s followed by progressive modest reductions. A Eicosapentaenoic Acid; ERK: Extracellular Signal Regulated Kinase; meta-analysis by the CDC has reported nearly 45% falling deaths from ET: Endothelin; FAS: Fatty Acid Synthase; FBG: Fibrinogen; FH: CVD (e.g., myocardial infarction (MI), heart failure (HF), unstable/ Familial Hypercholesterolemia; FIIa: Thrombin; FOXO: Forkhead Box chronic angina) in US between 1980 and 2000 [1], which is followed O; GAS6: Growth Arrest-Specific 6 Protein; GC: Gallocatechin; GI: by an unchanging/flattening trend of cardiovascular mortality Gastrointestine; GLP-1: Glucogan-Like Protein-1; GP: Glycoprotein; thereafter. The cardioprotection has been almost equally attributed GPIHBP1: Glycosylphosphatidylinositol-Anchored High-Density to pharmaceutical treatments (47%) and risk-factor reductions (44%) Lipoprotein Binding Protein 1; GPx1: Glutathione Peroxidase 1; [1]. The treatments have resulted from resuscitation, thrombolysis, GSH: Reduced Glutathione; GSK3β: Glycogen Synthase Kinase 3β; aspirin, statins, β- blockers, ACE inhibitors, warfarin, etc. while Hb: Hemoglobin; HDL: High Density Lipoprotein; HDL-C: HDL- lifestyle changes have involved initial and primary cardioprotection. Cholesterol; HF: Heart Failure; HIF: Hypoxia Inducible Factor; The reduced prevalence of major CVD a risk has included reductions HMGB1: High Mobility Group Box 1; HO-1: Heme Oxygenase-1; in total cholesterol, systolic blood pressure, smoking, and physical HSL: Hormone Sensitive Lipase; HSYA: Hydroxysafflor Yellow A; inactivity. However, increases in MBI and diabetes have hiked the Hyper TG: Hypertriglyceridemia; I/R: Ischemia/Reperfusion; Idol: deaths by 8% and 10%, respectively. Inducible Degrader Of LDLR; IFN: Interferon; IκB: Inhibitor Kappa B; IKK: IκB Kinase; IL: Interleukin; iNOS: Inducible NOS; IRS: Similarly, National Health and Nutrition Examination Survey [2] Insulin Receptor Substrate; IsoP: Isoprostane; JAK: Janus Kinase; revealed significant decreases in overall prevalence of coronary heart JNK: Jun N-Terminus Kinase; LDL: Low Density Lipoprotein; disease (CHD) from 10.3% to 8.0% in the US population between LDL-C: LDL-Cholesterol; LDLR: LDL Receptor; LMWH: Low- 2001 and 2012 among aged >40 years, which included angina and Molecular-Weight Heparin; Lp[a]: Lipoprotein [a]; LPL: Lipoprotein MI declines from 7.8% to 5.5% and from 5.5% to 4.7%, respectively. Lipase; LV: Left Ventricular; LX: Lipoxin; mAB: Monoclonal It is also proposed that a healthy lifestyle (no current smoking, Antibody; MAPK: Mitogen-Activated Protein Kinase; MCP-1: no obesity, regular physical activity, and a healthy diet) could offset Monocyte Chemoattractant Protein 1; MI: Myocardial Infarction; an elevated genetic risk for coronary artery disease. Diet is one of miR: MicroRNA; MMP: Matrix Metalloproteases; mTORC: modifiable CVD risk factors; it becomes the first consideration for Mammalian/Mechanistic Target Of Rapamycin Complex; MTP: cardiovascular health. Accordingly, dietary therapy is the first line Microsomal Triglyceride Transfer Protein; MΦ: Macrophage ; NFAT: prior to any medication. Typical nutritional modifications of CVD Nuclear Factor Activated T; NFkB: Nuclear Factor Kappa B; NLRP: risk factors could involve enhanced endothelial NO production NOD-Like Receptor Protein; NOS: Nitric Oxide Synthase; NOX: (by arginine, antioxidants: CoQ10, lipoic acid, vitamin C/E, NADPH Oxidase; Nrf2: Nuclear Factor Erythroid 2-Related Factor glutathione, and eNOS cofactors: B2, B3, BH4, folate), protection 2; NSAID: Non-Steroid Anti-Inflammatory Drug; NT-ProBNP: from LDL oxidation (by antioxidants, vitamin C/E, β-carotene), lipid N-Terminal Pro–Brain Natriuretic Peptide; OxLDL: Oxidized lowering (by conjugated linoleic acid, n-3 FAs), and lowered plasma LDL; PAF: Platelet Activating Factor; PAI: Plasminogen Activator homocysteine (by B6, B12, folate) [3]. For instance, B3 not only Inhibitor; PAR: Protease-Activated Receptor; PCSK: Proprotein increases HDL-C by 30%, but also significantly lowers lipoprotein [a] Convertase Subtilisin Kexin; PDE: Phosphate Diesterase; PGC-1α: (Lp[a]). Peroxisome Proliferator-Activated Receptor Coactivator; PGE2: Prostaglandin E2; PGI2: Prostacyclin; PI3K: Phosphatidylinositol The French paradox certainly underscores the benefits of 3-Kinase; PPAR: Peroxisome Proliferator-Activated Receptor; PT: phytochemicals (e.g., polyphenols) in cardioprotection; ever since, Partial Thrombin Time; PTEN: Phosphatase and Tensin Homolog; it has surged in-depth basic research and clinical trials for diverse RAAS: Rennin-Angiotensin-Aldosterone-System; RCT: Reverse disease prevention and intervention beyond CVD including cancers, Cholesterol Transport; ROS: Reactive Oxygen Species; Rv: Resolving; diabetes, neurodegenerative and inflammatory diseases, etc. This SCFA: Short Chain Fatty Acid; sGC: Soluble Guanylate Cyclase; review briefly summaries major CVD types, risks, and typical SirT: Sirtuins; SOD: Superoxide Dismutase; SREBP: Sterol Response pharmacological treatments followed by reviewing polyphenols, Submit your Manuscript | www.austinpublishinggroup.com Austin J Cardiovasc Dis Atherosclerosis 5(1): id1034 (2018) -