TGF-β and FRF-21: association with coronary artery disease in patients with type 2 diabetes and obesity

Backgraund: Obesity and type 2 diabetes mellitus (T2DM) are associated with with an increased risk of cardiovascular disease (CVD) and coronary artery disease (CAD), in particular.

Obesity lead to several fibrotic processes, including activation of transforming growth factor β (TGF-β). Recent data indicate the involvement of Fibroblast growth factor 21 (FGF-21) as an important metabolic regulator, and even biomarker of metabolic changes in obesity and T2DM. Impact of metabolic dysregulation that accompany obesity and T2DM in CAD development remain a great challenge.

Aims: To study TGF-β and FGF-21 level in patients with obesity and T2DM.

Materials and methods: TGF-β and FGF-21 were identified in peripheral blood samples of 66 patients with obesity, aged 48-65 years. 1st group included 21 patients with CHD and T2DM; 2nd group (22 patients)- with T2DM and excluded CHD; 3rd group (20 patients) with normal glucose metabolism and excluded CHD.

Results: TGF-β was lower in patients with CHD (group 1) than in the group of "metabolically healthy" obesity (p=0.022).

TGF-β in patients with T2DM negatively correlated with LDL cholesterol (r=-0.426, p=0.038) the degree of internal carotid artery stenosis (r=-0.426, p=0.024). Patients with verified CHD had a negative correlation with the processes of heart muscle remodeling (thickness of the left ventricular posterior wall (r=- 0.386, p=0.029) interventricular septum (r=-0.335, p=0.031). All patients with obesity had significantly increased level of FGF-21 compared with the control group (p=0.031) FGF-21 positively correlated with BMI (r=0.473, p=0.033)

Conclusions: TGF-β has negative correlations with the factors that can influence prognosis and the severity of the CVD/. There were found correlations of FGF-21, TGF-β with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CAD.

obesity, diabetes mellitus, cardiovascular disease, transforming growth factor β, fibroblast growth factor

1. Kannel WB. Diabetes and Cardiovascular Disease. Jama. 1979;241(19):2035. doi: 10.1001/jama.1979.03290450033020.

2. Liu J-W, Liu D, Cui K-Z, et al. Recent advances in understanding the biochemical and molecular mechanism of diabetic cardiomyopathy. Biochemical and Biophysical Research Communications. 2012;427(3):441-443. doi: 10.1016/j.bbrc.2012.09.058.

3. Eto K, Tumenbayar B, Nagashima S-i, et al. Distinct association of serum FGF21 or adiponectin levels with clinical parameters in patients with type 2 diabetes. Diabetes Research and Clinical Practice. 2010;89(1):52-57. doi: 10.1016/j.diabres.2010.03.019.

4. Xu A, Lin Z, Wu Z, et al. Serum Levels of FGF-21 Are Increased in Coronary Heart Disease Patients and Are Independently Associated with Adverse Lipid Profile. PLoS ONE. 2010;5(12):e15534. doi: 10.1371/journal.pone.0015534.

5. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF-β signaling in fibrosis. Growth Factors. 2011;29(5):196-202. doi: 10.3109/08977194.2011.595714.

6. Cavalera M, Wang J, Frangogiannis NG. Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities. Translational Research. 2014;164(4):323-335. doi: 10.1016/j.trsl.2014.05.001.

7. Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. The Lancet. 2006;368(9536):666-678. doi: 10.1016/s0140-6736(06)69251-9.

8. Oreopoulos A, McAlister FA, Kalantar-Zadeh K, et al. The relationship between body mass index, treatment, and mortality in patients with established coronary artery disease: a report from APPROACH. European Heart Journal. 2009;30(21):2584-2592. doi: 10.1093/eurheartj/ehp288.