The complex regulation of TGF-&amp;szlig; in cardiovascular disease

Redondo, Santiago; Navarro‐Dorado, Jorge; Ramajo, Marta; Medina, Úrsula; Tejerina, Teresa

doi:10.2147/vhrm.s28041

Cited by 28 publications

(33 citation statements)

References 86 publications

(106 reference statements)

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“…In atherosclerosis, TGF-β1 seems to lose its atheroprotective effects [2,5]. TGF-β1 exerts its wide variety of biological actions by means of very complex signaling pathways, some of which converge in the expression of the cell cycle regulatory protein p27 [3,4].…”

Section: Discussionmentioning

confidence: 99%

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

Redondo

Navarro‐Dorado

Ramajo

et al. 2014

J Cardiothorac Surg

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BackgroundTransforming growth factor beta (TGF-β1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-β1 signaling is affected by age.MethodsVascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-β1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n = 13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-β1 was determined by ELISA of cell-conditioned media.ResultsIn VSMC from aged patients we observed a lower TGF-β1 secretion, measured as TGF-β1 concentration in cell conditioned medium (p < 0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-β1 levels in CABG patients (p = 0.0195).ConclusionsVSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling.

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Section: Discussionmentioning

confidence: 99%

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

Redondo

Navarro‐Dorado

Ramajo

et al. 2014

J Cardiothorac Surg

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“…Finally, the TGF-β family is large and has multiple effects on vascular smooth muscle and endothelial cells. Both measured elevations and reductions in TGF-β have been reported to be involved in vascular pathology [24]. …”

Section: Discussionmentioning

confidence: 99%

“…This finding remains significant after having accounted for traditional risk factors, including age and history of CVD. We and others [2,3,24,28] have shown that DKD patients as an entire cohort are at greater mortality risk than CKD of other etiologies. In addition, we now demonstrate that biomarkers associated with a variety of different vascular pathophysiological processes may aid in identifying patients within the DKD group who are at highest risk of death before dialysis.…”

Section: Discussionmentioning

confidence: 99%

“…The biomarker profiles included markers of cardiac pathology such as left ventricular hypertrophy (fibroblast growth factor-23 [FGF23]), volume overload and myocardial stretch (troponin T, NT-proBNP), vascular stress and endothelial dysfunction (transforming growth factor [TGF]-beta, asymmetric dimethylarginine [ADMA]), and cardiac or all-cause mortality (FGF23, interleukin [IL]-6, ADMA) [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24]. A 1-year analysis of the whole CanPREDDICT cohort showed that the baseline measurement of biomarker profiles might aid in predicting mortality [25].…”

Section: Introductionmentioning

confidence: 99%

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The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality

Langsford

Tang²,

Hassan

et al. 2017

Am J Nephrol

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Background: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality. Methods: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). Results: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m² and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). Conclusions: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

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“…Recent evidence suggests that the modulation of immune responses is a promising approach for the prevention and treatment of atherosclerosis . TGF‐β1 pathway has been shown to be upregulated in a variety of immune disorders, including atherosclerosis . Therefore, we hypothesized that RGS3 regulates TGF‐β1 pathway to inhibit inflammation and atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

RGS3 inhibits TGF‐β1/Smad signalling in adventitial fibroblasts

Liu

Shi

et al. 2017

Cell Biochemistry & Function

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Recent evidence suggests that adventitial fibroblasts (AFs) are crucially implicated in atherosclerosis. However, the mechanisms by which AFs are dysfunctional and contribute to atherosclerosis remain unclear. This study aimed to investigate the role of regulator of G-protein signalling 3 (RGS3) in the regulation of AFs using apoE knockout mouse as the model. Pathological changes in aortic arteries of apoE knockout mice fed with hyperlipid diet were examined by Movat staining. The expression of RGS3, α-SMA, TGF-β1, Smad2, and Smad3 in the adventitia was detected by immunohistochemistry. Adventitial fibroblasts were isolated from aortic arteries of apoE knockout mice and infected with RGS3 overexpression lentivirus or empty lentivirus. The expression of RGS3, α-SMA, TGF-β1, Smad2, and Smad3 in AFs was detected by real-time polymerase chain reaction and Western blot analysis. We found that hyperlipidic diet caused significant aortic intima thickening and atherosclerotic plaques in 15-week-old apoE knockout mice. Compared to wild-type mice, RGS3 expression was lower while α-SMA, TGF-β1, Smad2, and Smad3 expression was higher in the adventitia of apoE knockout mice. In addition, lentivirus mediated overexpression of RGS3 caused decreased expression of α-SMA, TGF-β1, Smad2, and Smad3 in AFs derived from apoE(-/-) mice. In conclusion, these results suggest that RGS3 may provide protection against pathological changes of AFs and the development of atherosclerosis by inhibiting TGF-β1/Smad signalling. RGS3 may be a potential therapeutic target for atherosclerosis.

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The complex regulation of TGF-ß in cardiovascular disease

Cited by 28 publications

References 86 publications

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality

RGS3 inhibits TGF‐β1/Smad signalling in adventitial fibroblasts

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