Thymosin Beta-4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction (original) (raw)
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Physiological Research, 2008
Both, severe hypo- or hyperthyroidism may alter hemodynamic parameters. The aim of our study was to ascertain, whether also distinct changes within normal range of free thyroxine (fT4) would be associated with an impairment of left ventricle function in patients with chronic heart failure. Hundred-forty-eight patients (m121, f27, mean age 63.8±1.14 years) with chronic heart failure, fT4 levels within the normal range (9-22 pmol/l) and without thyrostatics or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Patients with fT4 in the range 11.9-14.6 pmol/l [optimal, 2nd-3th quintile] had significantly lower NT-proBNP (718±70.4 pg/ml), than those with fT4< 11.8 [low-normal, bottom quintile](1236±223.6 pg/ml; p<0.03) and those with fT4 over 14.6 pmol/l [high-normal, top two quintiles] (1192±114.9 pg/ml; p<0.0002). These differences remain significant, also if adjusted for age, gender and...
Thymosin beta-4 A/T polymorphism and acute coronary syndrome risk
ARCHIVES OF CLINICAL AND EXPERIMENTAL MEDICINE, 2019
Aim: Acute coronary syndrome (ACS) describes all the clinical conditions due to myocardial infarction that is caused by decreased blood flow in the coronary artery. Thymosin beta-4 (Tβ4) plays a significant role in the recovery of damaged tissues and promoting the survival of cardiomyocytes in ACS. In this study, it was aimed to determine the Tβ4 A/T (rs75112573) variation in ACS and its effects on the disease. Methods: This was a prospective case-control study. Forty-eight patients with ACS and 45 healthy controls were recruited for this study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).
ESC Heart Failure, 2021
Background We sought to examine clinical characteristics and outcomes in patients hospitalized for acute heart failure (HF) and thyrotoxicosis. Methods Patients with thyrotoxic HF were compared with age and gender-matched patients hospitalized for acute HF (controls). Thyr-HF was defined by the Framingham criteria for HF and clinical hyperthyroidism. Thyrotoxic cardiomyopathy was defined as left ventricular ejection fraction (LVEF) < 55%. Results Of 11 109 consecutive patients hospitalized for acute HF between 1 January 2002 and 1 January 2017, 92 patients (0.8%) had thyrotoxic HF. Clinical and echocardiographic data were available in 87 patients (age 51 ± 16 years; 74% female), representing the study population. Compared with controls, patients with Thyr-HF had a smaller body surface area (BSA), a higher LVEF, a lower LV end-diastolic diameter, a higher tricuspid annular plane systolic excursion (TAPSE), higher blood pressure, higher heart rate, and were more likely to have right-sided HF at presentation (P < 0.01 for all). The survival rate among patients with thyrotoxic HF was higher than the control group (HR: 4.3; 95% CI: 2.1-9.5). Fifty-eight percent of patients with thyrotoxic HF had thyrotoxic cardiomyopathy. In multivariate analysis, TAPSE (OR = 46; 95% CI: 1.04-2008.20; P = 0.047) and leukocytosis (OR = 16; 95% CI 1.01-259.39; P = 0.049) correlated with thyrotoxic cardiomyopathy. LV recovery was observed in 69% of these patients. Conclusions Thyrotoxic HF was uncommon among patients hospitalized for acute HF. However, after definitive therapy, these patients had a more favourable prognosis than those hospitalized for acute HF without thyrotoxic HF. Clinical phenotypes of thyrotoxic HF include small BSA, middle-aged female, HF-pEF, and right-sided HF. Thyrotoxic cardiomyopathy affected over half of the patients with thyrotoxic HF with a two-third recovery rate.
Cardioprotection by systemic dosing of thymosin beta four following ischemic myocardial injury
Frontiers in Pharmacology, 2013
Thymosin beta 4 (Tβ4) was previously shown to reduce infarct size and improve contractile performance in chronic myocardial ischemic injury via two phases of action: an acute phase, just after injury, when Tβ4 preserves ischemic myocardium via antiapoptotic or anti-inflammatory mechanisms; and a chronic phase, when Tβ4 activates the growth of vascular or cardiac progenitor cells. In order to differentiate between the effects of Tβ4 during the acute and during the chronic phases, and also in order to obtain detailed hemodynamic and biomarker data on the effects of Tβ4 treatment suitable for use in clinical studies, we tested Tβ4 in a rat model of chronic myocardial ischemia using two dosing regimens: short term dosing (Tβ4 administered only during the first 3 days following injury), and long term dosing (Tβ4 administered during the first 3 days following injury and also every third day until the end of the study). Tβ4 administered throughout the study reduced infarct size and resulted in significant improvements in hemodynamic performance; however, chamber volumes and ejection fractions were not significantly improved. Tβ4 administered only during the first 3 days following injury tended to reduce infarct size, chamber volumes and improve hemodynamic performance. Plasma biomarkers of myocyte injury were significantly reduced by Tβ4 treatment during the acute injury period, and plasma ANP levels were significantly reduced in both dosing groups. Surprisingly, neither acute nor chronic Tβ4 treatment significantly increased blood vessel density in peri-infarct regions. These results suggest the following: repeated dosing may be required to achieve clinically measureable improvements in cardiac function post-myocardial infarction (MI); improvement in cardiac function may be observed in the absence of a high degree of angiogenesis; and that plasma biomarkers of cardiac function and myocardial injury are sensitive pharmacodynamic biomarkers of the effects of Tβ4.
2008
aUnidad de Proteómica, Centro Nacional de Biotecnología/CSIC, Campus de Cantoblanco, E-28049 Madrid. Spain, bServicio de Inmunología. Fundación Jiménez Díaz. Madrid, cDepartamento Fisiopatologia Vascular, Hospital Nacional de Paraplejicos, SESCAM, Toledo. Spain, dDepartamento Cardiología, Hospital de Fuenlabrada, Madrid, Spain, eDepartamento Cardiología, Fundacion Jimnez Diaz, Madrid, Spain, fDepartamento Cardiología, Fundacion Hospital de Alcorcon, Madrid, Spain, gDepartamento de Patología Renal, Fundacion Jiménez Diaz, Madrid, Spain
Thymosin β4 and cardiac protection: implication in inflammation and fibrosis
Annals of the New York Academy of Sciences, 2012
Thymosin beta 4 (T4) is a ubiquitous protein with diverse biological functions. The effecter molecules targeted by T4 in cardiac protection remain unknown. We summarize previously published work showing that treatment with T4 in the myocardial infarction setting improves cardiac function by activating Akt phosphorylation, promoting the ILK-Pinch-Parvin complex, and suppressing NF-B and collagen synthesis. In the presence of Wortmannin, T4 showed minimal cardiac protection. In vitro findings revealed that pretreatment with T4 resulted in reduction of intracellular ROS in the cardiac fibroblasts and was associated with increased expression of antioxidant enzymes, reduction of Bax/Bcl 2 ratio, and attenuation of profibrotic genes. Silencing of Cu/Zn-SOD, catalase, and Bcl 2 genes abrogated the protective effect of T4. Our findings suggest that T4 improves cardiac function by enhancing Akt and ILK activation and suppressing NF-B activity and collagen synthesis. Furthermore, T4 selectively upregulates catalase, Cu/Zn-SOD, and Bcl 2 , thereby protecting cardiac fibroblasts from H 2 O 2 -induced oxidative damage. Further studies are warranted to elucidate the signaling pathway(s) involved in the cardiac protection afforded by T4.
The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence
Heart Failure Reviews, 2008
Thyroid hormone (TH) has a fundamental role in cardiovascular homeostasis in both physiological and pathological conditions, influencing cardiac contractility, heart rate (HR), diastolic function and systemic vascular resistance (SVR) through genomic and non-genomic mediated effects. In heart failure (HF) the main alteration of thyroid function is referred to as ''low-triiodothyronine (T3) syndrome'' (LT3S) characterized by decreased total serum T3 and free T3 (fT3) with normal levels of thyroxine (T4) and thyrotropin (TSH). Even if commonly interpreted as an adaptive factor, LT3S may have potential negative effects, contributing to the progressive deterioration of cardiac function and myocardial remodeling in HF and representing a powerful predictor of mortality in HF patients. All these observations, together with the early evidence of the benefits of T3 administration in HF patients indicate that placebo-controlled prospective studies are now needed to better define the safety and prognostic effects of chronic treatment with synthetic TH in HF.