The Role of CD36 in Cardiovascular Disease: A Critical Review | Chapter 4 | Recent Updates in Disease and Health Research Vol. 3

CD36, also known as the scavenger receptor B2, is a multifunctional receptor widely expressed in various organs. CD36 is expressed in various tissues, including endothelial cells, cardiac muscle cells, renal tubular epithelial cells, liver cells, adipocytes, platelets, and macrophages, and is involved in many pathophysiological processes, including immune regulation and metabolic regulation. CD36 plays a crucial role in the uptake of long-chain fatty acids, the main metabolic substrate in myocardial tissue. The maturation and transportation of CD36 is regulated by post-translational modifications, including phosphorylation, ubiquitination, glycosylation, and palmitoylation. CD36 is decreased in pathological cardiac hypertrophy caused by ischaemia–reperfusion and pressure overload, and increased in diabetic cardiomyopathy and atherosclerosis. Deficiency of CD36 alleviates diabetic cardiomyopathy and atherosclerosis, while overexpression of CD36 eliminates ischaemia–reperfusion damage, together suggesting that CD36 is closely associated with the progression of cardiovascular diseases and may be a new therapeutic target. Transcriptional activation, post-translational modification, and localization changes of CD36 may provide new directions for the treatment of cardiovascular diseases. This review summarizes the regulation and post-translational modifications of CD36 and evaluates its role in cardiovascular diseases and its potential as a therapeutic target.

Author(s) Details:

Hongyang Shu,
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan-430000, China.

Yizhong Peng,
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China.

Weijian Hang,
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan-430000, China.

Jiali Nie,
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan-430000, China.

Ning Zhou,
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan-430000, China.

Dao Wen Wang,
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan-430000, China and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan-430000, China.

Please see the link here: https://stm.bookpi.org/RUDHR-V3/article/view/13548

Study about Mir15a/Mir16-1 Cluster and Its Novel Targeting Molecules Negatively Regulate Cardiac Hypertrophy | Chapter 10 | Advancement and New Understanding in Medical Science Vol. 3

In this study, we screened hypertrophic-associated miR-NAs. We demonstrate the mir15a/mir16-1 cluster is negatively correlated with the degree of cardiac hypertrophy in patients with HCM. Additionally, CCAAT/enhancer binding protein (C/EBP)  β is responsible for its down- regulation in CMs by directly binding to its promoters. In response to pathological stimuli, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. miRNAs are increasingly recognized as pathogenic factors, clinically relevant biomarkers, and potential therapeutic targets. We identified that mir15a/mir16-1 cluster was negatively correlated with hypertrophic severity in patients with hypertrophic cardiomyopathy. The mir15a/mir16-1 expression was enriched in cardiomyocytes (CMs), decreased in hypertrophic human hearts, and decreased in mouse hearts after transverse aortic constriction (TAC). CM-specific mir15a/mir16-1 knockout pro- moted cardiac hypertrophy and dysfunction after TAC. CCAAT/enhancer binding protein (C/EBP) β was responsible for the downregulation of mir15a/mir16- 1 cluster transcription. Mechanistically, mir15a/mir16-1 cluster attenuated the insulin/IGF1 signal transduction cascade by inhibiting multiple targets, including INSR, IGF-1R, AKT3, and serum/glucocorticoid regulated kinase 1 (SGK1). Pro-hypertrophic response induced by mir15a/mir16-1 inhibition was abolished by knockdown of insulin receptor (INSR), insulin like growth factor 1 receptor (IGF1R), AKT3, or SGK1. In vivo systemic delivery of mir15a/mir16-1 by nanoparticles inhibited the hypertrophic phenotype induced by TAC. Importantly, decreased serum mir15a/mir16-1 levels predicted the occurrence of left ventricular hypertrophy in a cohort of patients with hypertension. Therefore, mir15a/mir16-1 cluster is a promising therapeutic target and biomarker for cardiac hypertrophy. Nanoparticle-carrying mir15a/mir16-1 treatment decreases cardiac hypertrophy and improves cardiac function in an experimental animal model of pressure overload. Our study exhibits important clinical implications for both the treatment and prediction of cardiac hypertrophy.

mir15a/mir16-1 cluster exerts protective effects against the progression of the car- diac hypertrophy and dysfunction (left). During hypertrophic stress, increased C/EBP β downregulates the mir15a/mir16-1 cluster, resulting in up-regulation of multiple target proteins (INSR, IGF1R, AKT3, SGK1) in cardiomyocytes, causing increased activation of insulin/IGF1 signaling, ultimately causing car- diac hypertrophy and dysfunction. The CHO-PEGA delivery system replenishes mir15a/mir16-1 in the heart, attenuating cardiac hypertrophy and heart failure (right). Meanwhile, reduced circulating mir15a/mir16-1 levels are associated with the hypertrophic degree and cardiac hypertrophy risk in patients (bottom).

Author(s) Details:

Hongchang Guo,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Ke Ma,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Wenjing Hao,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Yao Jiao,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Ping Li,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Jing Chen,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Chen Xu,
State Key Laboratory of Chemical Resource Engineering, and Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China.

Fu-jian Xu,
State Key Laboratory of Chemical Resource Engineering, and Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China.

Wayne Bond Lau,
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.

Jie Du,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Xin-liang Ma,
Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.

Yulin Li,
Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.

Please see the link here: https://stm.bookpi.org/ANUMS-V3/article/view/13165