Increased Transforming Growth Factor‐β Levels Associated With Cardiac Adverse Events in Hypertrophic Cardiomyopathy

Abstract

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease characterized by ventricular hypertrophy, myocardial fibrosis, and impaired ventricular relaxation. The exact mechanisms by which fibrosis is caused remain unknown. Hypothesis: Circulating TGF-β is related to poor prognosis in HCM. Methods: We compared TGF-β levels of 49 HCM patients with those of 40 non-HCM patients. We followed the patients with HCM for 18 months and divided them into 2 groups: low TGF-β (≤4877 pg/mL) and high TGF-β (>4877 pg/mL). We compared the 2 groups in terms of brain natriuretic peptide (BNP), echocardiographic parameters, and clinical outcomes including myocardial infarction, arrhythmias, implantable cardioverterdefibrillator implantation, hospitalization, New York Heart Association (NYHA) class, acute heart failure, and mortality. Results: The HCM patients had higher TGF-β levels than those in the control group (P = 0.005). In the follow-up, those in the high TGF-β group had higher BNP levels, larger left-atrial size, thicker interventricular septum, NYHA class, more hospitalizations, and a greater number of clinical adverse events (P < 0.001, P = 0.01, P < 0.001, P = 0.002, P < 0.001 and P = 0.003, respectively). TGF-β level of >4877 pg/mL can predict adverse events with a specificity of 75% and a sensitivity of 72% (P = 0.014). In multivariate regression analysis, TGF-β, BNP, and interventricular septum thickness were significantly associated with adverse events (P = 0.028, P = 0.030, and P = 0.034, respectively). Conclusions: The TGF-β level is higher in HCM patients and associated with a poor prognosis in HCM.

Ginkgo biloba extract prevents acute myocardial infarction and suppresses the inflammation- and apoptosis-regulating p38 mitogen-activated protein kinases, nuclear factor-κB and B-cell lymphoma 2 signaling pathways

“…Dynamic changes in the ECM occur following AMI and has an important role in ventricular remodeling. During the period of AMI, transforming growth factor in cardiac muscle tissue of TGF-β promoting fibrosis factor is activated (21). The fibrosis cell generates into type I and type III collagenous fibers, which gradually develop into scar tissue.…”

FGF23 promotes myocardial fibrosis in mice through activation of β-catenin

“…TGF-β can increase expression of collagen I/III by stimulating the synthesis and deposition of collagen, fibronectin, proteoglycan and other intercellular substances. Over-expression of TGF-β has been demonstrated to be a common pathway for different pathological factors leading to myocardial fibrosis [ 12 - 14 ]. Another pro-fibrotic gene, β-catenin has been demonstrated to have crosstalk with TGF-β, [ 11 , 15 , 16 ] which is complex and context-dependent, [ 16 ] while our previous study demonstrated that fractalkine (FKN) plays an important role in the promotion of myocardial fibrosis and cardiac remodeling via up-regulating matrix metallopeptidase 9, procollagen I and III, and TGF-β.…”

Clinical significance of different assesment methods of myocardial fibrosis in patients with hypertrophic cardiomyopathy.

“…Он оказывает стимулирую щее действие на клетки мезенхимального происхожде ния (фибробласты, тучные клетки, адипоциты) и облада ет ингибирующим действием на клетки эпителиальной (эндотелий) и нейроэктодермальной природы. У обсле дованных нами пациентов с ГКМП выявлен повышен ный уровень TGFβ1, что согласуется с ранее опублико ванным исследованием, в котором повышенный уровнь TGFβ1 имели пациенты с ГКМП с более высоким ФК СН, более высоким уровнем натрийуретического пепти да и более частыми повторными госпитализациями [8]. Таким образом, повышенный уровень TGFβ1 может служить прогностическим фактором неблагоприятных событий у пациентов с ГКМП.…”