Received: 13 October 2018 | Accepted: 16 November 2018 DOI: 10.1002/jcp.27935 MINI ‐ REVIEW T‐bet transcription factor in cardiovascular disease: Attenuation or inflammation factor? Habib Haybar 1 | Hadi Rezaeeyan 2 | Mohammad Shahjahani 2 | Reza Shirzad 2 | Najmaldin Saki 2 1 Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2 Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Correspondence Najmaldin Saki, Thalassemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Email: najmaldinsaki@gmail.com Abstract T‐bet is a major transcription factor increasing inflammatory responses in the immune system. Recently, it has been shown that this factor leads to inflammation in cardiovascular disease (CVD). In this study, we examine the dual role of T‐bet in inducing and suppressing inflammatory reactions as well as angiogenesis induction due to inflammatory cytokines in CVD. Relevant literature was identified by a Pubmed search (1992–2018) of English‐language papers using the terms “T‐bet,” “Cardiovascular disease,”“Immune response,” and “Angiogenesis.” Although T‐bet causes differentiation of Th1 cells and activation of immune cells such as NK and DC, it suppresses inflammatory responses and replaces damaged vessels with new ones by activating regulatory T‐cells and stimulating angiogenesis. It can be stated that T‐bet acts as double‐edged sword. Therefore, the identification of pathways that can increase the function of T‐bet in activating Tregs and inducing angiogenesis might be used as a new therapeutic option in future investigations. HIGHLIGHTS • T‐bet factor plays an essential role in the regulation of immune responses in CVD. • T‐bet factor induces angiogenesis through the mediation of inflammatory cytokines. • T‐bet can be effective in CVD pathogenesis via interaction with other transcription factors. KEYWORDS angiogenesis, cardiovascular disease, immune response, T‐bet 1 | INTRODUCTION Cardiovascular disease (CVD) is a common disease with high mortality rates in the world today. Several factors have been identified that contribute to the development of CVD (Peng, Xiao, Hu, & Zhang, 2018). However, the main cause of CVD has not been determined. The results of recent studies have shown that inflammatory responses and impairment of immune function play important roles in the incidence of CVD (Ahearn, Shields, Liu, & Manzi, 2015). In several CVDs, including heart failure (HF) and atherosclerosis, inflammation leads to the progression of disease by impairing cardiac cells and activating effector immune cells (e.g., TCD4 + ), which causes the release of different chemokines and cytokines (Haybar, Shahrabi, Rezaeeyan, Shirzad, & Saki, 2018; Su et al., 2015; Zhao et al., 2011). Innate and adaptive immune responses are involved in the activation of T‐cells (Wu et al., 2018), and TCD4 + cells are seemingly the most important cells that play a role in CVD pathogenesis. However, the differentia- tion rate of T‐cells to T helper1 (Th1) or Th2 cells is likely to determine J Cell Physiol. 2018;1–8. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1