Mechanotransduction regulates inflammation responses of epicardial adipocytes in cardiovascular diseases

Figures

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  Figure 1. The cellular origins of cardiac adipocytes. PAT is situated between the visceral and parietal pericardium, which derived from the primitive thoracic mesenchyme and is vascularized by blood from the thoracic vasculature. EAT is located between the myocardium and the epicardium, mainly deriving from Wt1-expressing mesothelial cells. IAT is observed in the subendocardium in postnatal mouse hearts; both PDGFRa+ and PDGFRb+ cells, but not NG2+ pericytes, contribute to intramyocardial adipocytes during postnatal heart development and homeostasis. PDGFRa+, platelet-derived Growth Factor Receptors a+; PDGFRb+, platelet-derived growth Factor Receptors b +; neural-glial antigen 2+, NG2+; PAT, pericardial cardiac adipocytes; EAT, epicardial cardiac adipocytes; IAT, intramyocardial adipose tissues; TGF-β, transforming growth factor-beta; FGFs, fibroblast growth factors; PPARγ, peroxisome proliferator-activated receptor gamma; Wt1, Wilms tumor gene 1.

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  Figure 2. The molecular signaling interplay between the adipose tissue and cardiomyocytes. The epicardial adipose tissue (EAT) lies on the surface of the human heart inside the visceral pericardium, and interacts with adjacent cardiomyocytes and extracellular matrix in a paracrine manner. EAT interacts with the cardiovascular system by releasing amounts of cytokines, including leptin, adiponectin, resistin, apelin, nitric oxide, interleukins, tumor necrosis factor-a (TNF-a), and other inflammatory factors. These EAT-derived molecules are involved in several biological processes in the myocardium, such as oxidative stress, cardiac inflammation, fibrosis, and cardiac metabolism. In addition to these outside-to-inside signals, vascular inflammation and oxidative stress can also affect adipose tissue biology in an inside-to-outside manner. PAT, Pericardial Adipose Tissue; ERK1/2, extracellular signal-regulated kinases 1/2; Jak2/STAT3, Janus kinase 2/signal transducer and activator of transcription 3; Rho/ROCK, Ras homolog gene family member; PI3K/Akt, phosphoinositide 3-kinase/protein kinase B; PKC, protein kinase C; NO, nitric oxide; TNF, tumor necrosis factor; eNOS, endothelial nitric oxide…

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  Figure 3. The molecular signaling of mechanotransduction in adipocytes. The molecular signaling of mechanotransduction in adipocytes includes focal adhesion kinase (YAP)/transcriptional coactivator with PDZ‐binding motif (TAZ), Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), Ras Homolog Family Member A/Rho-Associated Protein Kinase (RhoA/ROCK), and transforming growth factor β1 (TGF-β1)/Smad signaling pathway. Moreover, mechanical stimuli mediate adipose differentiation. YAP/TAZ signaling pathway enhances adipogenesis; MAPK/ERK, RhoA/ROCK, and TGF-β1/Smad signaling pathway inhibit adipogenesis. ECM, extracellular matrix; Mst, mammalian ste20-like protein kinase; LATS1/2, large tumor suppressor 1 and 2; MOB1, MOB kinase activator 1; SAV1, Sav family containing protein 1; YAP/TAZ, yes-associated protein)/transcriptional co-activator with PDZ binding motif; TEAD, members of the TEA domain; CDC42, Cell division control protein 42; ERK, extracellular signal-regulated kinase;MEKK, MAP kinase kinase kinase; TAK, TGF β-activated kinase; MKK, MAP kinase kinase; JNK, c-Jun N-terminal protein kinases; TCF, ternary complex factor; SRF, serum response factor; AP1,…