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The role of cardiac microenvironment in cardiovascular diseases: implications for therapy

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Abstract

Due to aging populations and changes in lifestyle, cardiovascular diseases including cardiomyopathy, hypertension, and atherosclerosis, are the leading causes of death worldwide. The heart is a complicated organ composed of multicellular types, including cardiomyocytes, fibroblasts, endothelial cells, vascular smooth muscle cells, and immune cells. Cellular specialization and complex interplay between different cell types are crucial for the cardiac tissue homeostasis and coordinated function of the heart. Mounting studies have demonstrated that dysfunctional cells and disordered cardiac microenvironment are closely associated with the pathogenesis of various cardiovascular diseases. In this paper, we discuss the composition and the homeostasis of cardiac tissues, and focus on the role of cardiac environment and underlying molecular mechanisms in various cardiovascular diseases. Besides, we elucidate the novel treatment for cardiovascular diseases, including stem cell therapy and targeted therapy. Clarification of these issues may provide novel insights into the prevention and potential targets for cardiovascular diseases.

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Abbreviations

IVIG:

Intravenous immunoglobulin

ECM:

Extracellular matrix

PDGFRα:

Platelet-derived growth factor receptor α

Ang II:

Angiotensin II

EndoMT:

Endothelial-to-mesenchymal transition

NO:

Nitric Oxide

ET-1:

Endothelin-1

iNOS:

Inducible nitric oxide synthase

HCM:

Hypertrophic cardiomyopathy

DCM:

Dilated cardiomyopathy

RCM:

Restrictive cardiomyopathy

ACM:

Arrhythmia Cardiomyopathy

SR:

Sarcoplasmic reticulum

RYR2:

Ryanodine receptor 2

SERCA:

Sarco/endoplasmic reticulum Ca2+-ATPase

cTnC:

Cardiac troponin C

FGF2:

Fibroblast growth factor 2

PDGF:

Platelet-derived growth factor

HF:

Heart failure

eNOS:

Endothelial nitric oxide synthase

ROS:

Reactive oxygen species

MI:

Myocardial infarction

MMPs:

Matrix metalloproteinases

DCs:

Dendritic cells

MSCs:

Mesenchymal stem cells

HSCs:

Hematopoietic stem cells

EPCs:

Endothelial progenitor cells

CSCs:

Cardiac stem cells

iPSCs:

Embryonic stem cells and induced pluripotent stem cells

bFGF:

Basic fibroblast growth factor

VEGF:

Vascular endothelial growth factor

LVEF:

Left ventricular ejection fraction

AdMSC:

Adipose-derived mesenchymal stem cell

VEGFR2:

Vascular endothelial growth factor receptor 2

hESCs:

Human embryonic stem cells

CAR-T:

Chimeric antigen receptor T cell

NHEJ:

Non-homologous terminal ligation

HDR:

Homologous recombinant repair

MYH6:

Myosin heavy chain 6

MYBPC3:

Myosin-binding protein C3

AAV:

Adeno-associated virus

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82170370, 81770381), the Natural Science Foundation of Jiangsu Province (BK20211165) and Zhishan Youth Scholar Program of SEU.

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Authors and Affiliations

  1. School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China

    Jiayu Yao, Yuejun Chen, Yuqing Huang & Xingjuan Shi

  2. Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China

    Xiaoou Sun

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Jiayu Yao: prepared the original draft. Yuejun Chen: designed and prepared the figures. Yuqing Huang: collected the literature. Xiaoou Sun: manuscript revision. Xingjuan Shi: manuscript design, supervision and revision. All authors read and approved the final manuscript.

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Yao, J., Chen, Y., Huang, Y. et al. The role of cardiac microenvironment in cardiovascular diseases: implications for therapy. Human Cell 37, 607–624 (2024). https://doi.org/10.1007/s13577-024-01052-3

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