Lacidipine attenuates TNF-α-induced cardiomyocyte apoptosis

Wang, Qiulin; Zhao, Lei; Feng, Na; Zhou, Peng; Wu, Qi; Fan, Rong; Li, Juan; Zhang, Shumiao; Wang, Yuemin; Xu, Xuezeng; Yu, Shuang; Pei, Jianming

doi:10.1016/j.cyto.2014.08.004

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…Koyani et al [70] reported that empagliflozin reduced the LPS-induced increase in TNF-α levels associated with increased AMPK phosphorylation. TNF-α is known to activate caspase-3 via the caspase-12 cascade to induce cardiomyocyte apoptosis [142]. In animal models of heart I/R injury and hepatorenal syndrome, early administration of SGLT2i was reported to downregulate cleaved caspase-3 [143,144], which is consistent with our expectations.…”

Section: Sglt2i and Myocardial Apoptosissupporting

confidence: 88%

Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Huang

Luo

Liao

et al. 2023

Cardiovasc Diabetol

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Among the complications of diabetes, cardiovascular events and cardiac insufficiency are considered two of the most important causes of death. Experimental and clinical evidence supports the effectiveness of SGLT2i for improving cardiac dysfunction. SGLT2i treatment benefits metabolism, microcirculation, mitochondrial function, fibrosis, oxidative stress, endoplasmic reticulum stress, programmed cell death, autophagy, and the intestinal flora, which are involved in diabetic cardiomyopathy. This review summarizes the current knowledge of the mechanisms of SGLT2i for the treatment of diabetic cardiomyopathy. Graphical Abstract

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Section: Sglt2i and Myocardial Apoptosissupporting

confidence: 88%

Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Huang

Luo

Liao

et al. 2023

Cardiovasc Diabetol

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“…Importantly, TAC-induced apoptosis was remarkably inhibited by TNFR1 KO, but facilitated by TNFR2 KO, suggesting that TNFR1 signaling mediated apoptosis. sTNF-α causes apoptosis of myocardial cells [25,26], but the role of tmTNF-α is unknown. We found that tmTNF-α-overexpressed in fixed 3T3 cells stimulated proliferation, instead of apoptosis, in H9C2 cells, which could be effectively prevented by TNFR2 KD (S5E and S5F Fig).…”

Section: Plos Biologymentioning

confidence: 99%

Transmembrane tumor necrosis factor alpha attenuates pressure-overload cardiac hypertrophy via tumor necrosis factor receptor 2

Miao

Zhou

et al. 2020

PLoS Biol

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Tumor necrosis factor-alpha (TNF-α) plays an important pathogenic role in cardiac hypertrophy and heart failure (HF); however, anti-TNF is paradoxically negative in clinical trials and even worsens HF, indicating a possible protective role of TNF-α in HF. TNF-α exists in transmembrane (tmTNF-α) and soluble (sTNF-α) forms. Herein, we found that TNF receptor 1 (TNFR1) knockout (KO) or knockdown (KD) by short hairpin RNA or small interfering RNA (siRNA) significantly alleviated cardiac hypertrophy, heart dysfunction, fibrosis, and inflammation with increased tmTNF-α expression, whereas TNFR2 KO or KD exacerbated the pathological phenomena with increased sTNF-α secretion in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro, respectively, indicating the beneficial effects of TNFR2 associated with tmTNF-α. Suppressing TNF-α converting enzyme by TNF-α Protease Inhibitor-1 (TAPI-1) to increase endogenous tmTNF-α expression significantly alleviated TAC-induced cardiac hypertrophy. Importantly, direct addition of exogenous tmTNF-α into cardiomyocytes in vitro significantly reduced ISO-induced cardiac hypertrophy and transcription of the pro-inflammatory cytokines and induced proliferation. The beneficial effects of tmTNF-α were completely blocked by TNFR2 KD in H9C2 cells and TNFR2 KO in primary myocardial cells. Furthermore, we demonstrated that tmTNF-α displayed antihypertrophic and anti-inflammatory effects by activating the AKT pathway and inhibiting the nuclear factor (NF)-κB pathway via TNFR2. Our data suggest that tmTNF-α exerts cardioprotective effects via TNFR2. Specific targeting of tmTNF-α processing, rather than anti-TNF therapy, may be more useful for the treatment of hypertrophy and HF.

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“…Other authors have found that, in chondrocytes, chemerin expression can be regulated by factors (such as IL-1β and LPS) implicated in inflammatory processes [78]. More studies are needed to elucidate the regulation of chemerin and CMKLR1 in cardiomyocytes, and the possible relation of the influence of TNF-α on chemerin to cardiac inflammation, cardiomyocyte apoptosis, and cardiac disease, serum chemerin being correlated not only with TNF-α but also with other components of metabolic syndrome and markers of inflammation such as C-reactive protein (CRP) and IL-6 [79], while TNF-α, which is implicated in several cardiovascular diseases, has been reported to mediate inflammation and apoptosis in HL-1 cardiomyocytes [80,81].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes

Rodríguez-Penas¹,

Feijóo‐Bandín²,

García-Rúa³

et al. 2015

Cell Physiol Biochem

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Background: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. Methods: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. Results: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. Conclusion: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin) and inflammatory (TNF-α) mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

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Lacidipine attenuates TNF-α-induced cardiomyocyte apoptosis

Cited by 7 publications

References 33 publications

Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Transmembrane tumor necrosis factor alpha attenuates pressure-overload cardiac hypertrophy via tumor necrosis factor receptor 2

The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes

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