Platelet expression of transforming growth factor beta 1 is enhanced and associated with cardiovascular prognosis in patients with acute coronary syndrome

被引：29

作者：

Rath, Dominik ^{[1
]}

Chatterjee, Madhumita ^{[1
]}

Mueller, Iris ^{[1
]}

Mueller, Karin ^{[1
]}

Boeckmann, Corinna ^{[1
]}

Droppa, Michal ^{[1
]}

Stimpfle, Fabian ^{[1
]}

Karathanos, Athanasios ^{[1
]}

Borst, Oliver ^{[1
]}

Seizer, Peter ^{[1
]}

Langer, Harald ^{[1
]}

Schwab, Matthias ^{[2
,3
]}

Gawaz, Meinrad ^{[1
]}

Geisler, Tobias ^{[1
]}

机构：

[1] Univ Tubingen, Med Klin 3, Tubingen, Germany

[2] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[3] Univ Tubingen Hosp, Dept Clin Pharmacol, Tubingen, Germany

来源：

ATHEROSCLEROSIS | 2014年 / 237卷 / 02期

关键词：

Transforming growth factor beta-1; Acute coronary syndrome; Coronary artery disease; Platelets; CARDIAC FIBROBLASTS; FIBROSIS; DYSFUNCTION; ACTIVATION;

D O I：

10.1016/j.atherosclerosis.2014.10.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background. Functional recovery and prognosis after acute coronary syndromes (ACS) are mainly driven by the extent of reperfusion injury and myocardial repair mechanisms. Transforming growth factor-beta 1 (TGF-beta 1) is critically involved in cardiac injury, repair and remodeling. In this study, we investigated the prognostic role of platelet TGF-b1 surface expression and circulating TGF-beta 1 levels in patients with coronary artery disease (CAD). Methods and results. Expression of TGF-beta 1 in platelets and circulating TGF-beta 1 levels were investigated by flow cytometry and ELISA, respectively, among patients with ACS and stable CAD undergoing percutaneous coronary intervention (PCI). In a cohort study, platelet and circulating TGF-beta 1 was measured in 299 patients with symptomatic CAD (stable CAD = 145, ACS = 154) at the time of PCI. The primary combined endpoint was defined as death and/or STEMI during 12-month follow-up. Platelets expressed TGF-beta 1 and circulating TGF-beta 1 showed a weak, but significant negative correlation. TGF-beta 1 surface expression was significantly elevated on platelets in ACS patients compared to patients with stable CAD (median MFI 13.4 vs. median MFI 11.7, p = 0.003). During follow-up, lower platelet expression of TGF-beta 1 was associated with all-cause mortality (median MFI 11.0 vs. median MFI 13.9, p = 0.011) as well as for the combined endpoint of death and/or STEMI, (median MFI 10.8 vs. median MFI 13.9, p = 0.006). In multivariate analysis platelet TGF-beta 1 expression was independently associated with the combined primary endpoint in the overall cohort (Hazard Ratio 0.31, 95% Confidence Interval 0.11-0.89, p = 0.029) and was strongly associated with prognosis in ACS patients. There was no significant association of circulating TGF-beta 1 levels neither with the presence of ACS nor the occurrence of the primary endpoint. Conclusion. These findings highlight a potential role of platelet expressed TGF-beta 1 in ACS and indicate a prognostic value of TGF-beta 1 on clinical outcomes in patients with acute coronary syndromes. Large scale studies are warranted to further evaluate the regulatory mechanisms of platelet TGF-beta 1 expression-and its prognostic impact in CAD. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：754 / 759

页数：6

共 35 条

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