Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor

Wang, Xiaoyu; McLennan, Susan V.; Allen, Terri J.; Tsoutsman, Tatiana; Semsarian, Christopher; Twigg, Stephen M.

doi:10.1152/ajpcell.00049.2009

Cited by 65 publications

(58 citation statements)

References 56 publications

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“…30, 31 In addition to stimulating collagen synthesis and causing fibroblast proliferation, 32 CTGF also induces hypertrophy and apoptosis in cardiomyocytes. 33 In this study, we found that CTGF expression was elevated in the atria of AF patients. We also demonstrated that after 1 h of Ang II perfusion, rat hearts rapidly expressed increased CTGF mRNA and protein expressions.…”

Section: Discussionmentioning

confidence: 54%

Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes

Hong

Hou

et al. 2011

Circ J

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Background: Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood. Methods and Results:Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs.Conclusions: AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling. (Circ J 2011; 75: 1592 - 1600

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Section: Discussionmentioning

confidence: 54%

Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes

Hong

Hou

et al. 2011

Circ J

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“…81 These CCN2 effects were shown to rely on the activity of the tyrosine kinase A receptor that has previously been implicated in CCN2-dependent signaling (Figure 1). 81 CCN2 silencing using small interfering RNA of activated primary cardiac fibroblasts resulted in strongly reduced expression of stretch-induced chemokines (Ccl2, Ccl7, and Ccl8), matrix metalloproteinases (MMP2 and MMP9), ECM (Col3a1), and a cell-to-cell contact protein (Cx43). 82 Ang-II-induced expression of hypertrophic marker genes or collagens was not affected by treatment with anti-CCN2 monoclonal antibodies, whereas anti-CCN2 monoclonal antibodies caused resistance to adverse LV remodeling and LV dysfunction in hearts resulting from pressure overload caused by thoracic aortic constriction.…”

Section: Ccn2mentioning

confidence: 82%

“…79,80 Expression of CCN2 mRNA is induced by both high glucose and palmitate in H9c2 cells and in mouse neonatal cardiomyocyte primary cultures. 81 Small interfering RNAs against CCN2 reduced the abilities of high glucose and palmitate to induce hypertrophy and apoptosis. 81 These CCN2 effects were shown to rely on the activity of the tyrosine kinase A receptor that has previously been implicated in CCN2-dependent signaling (Figure 1).…”

Section: Ccn2mentioning

confidence: 99%

“…81 Small interfering RNAs against CCN2 reduced the abilities of high glucose and palmitate to induce hypertrophy and apoptosis. 81 These CCN2 effects were shown to rely on the activity of the tyrosine kinase A receptor that has previously been implicated in CCN2-dependent signaling (Figure 1). 81 CCN2 silencing using small interfering RNA of activated primary cardiac fibroblasts resulted in strongly reduced expression of stretch-induced chemokines (Ccl2, Ccl7, and Ccl8), matrix metalloproteinases (MMP2 and MMP9), ECM (Col3a1), and a cell-to-cell contact protein (Cx43).…”

Section: Ccn2mentioning

confidence: 99%

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Getting to the Heart of the Matter

Leask

2015

Circulation Research

296

147

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Fibrotic diseases are a significant global burden for which there are limited treatment options. The effector cells of fibrosis are activated fibroblasts called myofibroblasts, a highly contractile cell type characterized by the appearance of α-smooth muscle actin stress fibers. The underlying mechanism behind myofibroblast differentiation and persistence has been under much investigation and is known to involve a complex signaling network involving transforming growth factor-β, endothelin-1, angiotensin II, CCN2 (connective tissue growth factor), and platelet-derived growth factor. This review addresses the contribution of these signaling molecules to cardiac fibrosis.

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“…Moreover, experimental diabetes mellitus leads to upregulation of profibrotic genes and fibrosis in the myocardium [26,27]. In the heart, connective tissue growth factor also appears as a mediator of adverse effects of high glucose and fatty acids in cardiomyocytes [28]. Interestingly, connective tissue growth factor has also been implicated in the epithelial-to-mesenchymal transition of renal tubular epithelial cells, which contributes to the renal fibrosis associated with diabetic nephropathy [29].…”

Section: Insulin Resistance and Fibrosismentioning

confidence: 99%

Obesity and Fatty Liver Are ‘Grease’ for the Machinery of Hepatic Fibrosis

Bosserhoff¹,

Hellerbrand

2011

Dig Dis

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Nonalcoholic fatty liver disease (NAFLD) starts with hepatic steatosis, which can progress with inflammation to nonalcoholic steatohepatitis, and a subset of patients develop progressive fibrosis and ultimately cirrhosis. In the majority of cases, NAFLD is associated with (components of) the metabolic syndrome. Obesity, diabetes and hepatic steatosis are also independent risk factors for hepatic fibrosis in different chronic liver diseases. However, the question is whether it is actually nonalcoholic steatohepatitis and not ‘simple’ steatosis that promotes fibrosis progression based on hepatocellular injury. In this review, the concept will be put forward that (1) hepatic steatosis per se is profibrogenic, and (2) that in NAFLD development and progression of hepatic fibrosis is not simply determined by (the degree of) hepatic inflammation. In addition to the liver, this view is expanded to other organs affected by the metabolic syndrome, which affects hepatic injury and fibrosis also via extrahepatic pathophysiological alterations. In conclusion, fatty liver and the metabolic syndrome, respectively, have to be recognized as significant lubricants of hepatic fibrosis, and simple hepatic steatosis cannot be considered as benign.

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Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor

Abstract: Wang X, McLennan SV, Allen TJ, Tsoutsman T, Semsarian C, Twigg SM. Adverse effects of high glucose and free fatty acid on cardiomyocytes are mediated by connective tissue growth factor.

Cited by 65 publications

References 56 publications

Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes

Elevated Expression of Connective Tissue Growth Factor in Human Atrial Fibrillation and Angiotensin II-Treated Cardiomyocytes

Getting to the Heart of the Matter

Obesity and Fatty Liver Are ‘Grease’ for the Machinery of Hepatic Fibrosis

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