Tribbles pseudokinases in cardiovascular diseases: Molecular mechanisms, genetic insights, and therapeutic prospects

Cardiovascular disease (CVD) represents a significant global public health challenge, with its high incidence and mortality rates imposing a substantial socioeconomic burden. Tribbles family proteins (TRIB1, TRIB2, and TRIB3), functioning as pseudokinases, play a pivotal role in the pathogenesis and progression of various CVDs, including coronary heart disease, heart failure, hypertension, cardiomyopathy, and pulmonary hypertension. The progression of CVD is modulated by the tribbles family proteins through key mechanisms such as the regulation of inflammatory responses, apoptosis, endoplasmic reticulum stress, and insulin signaling pathways. Furthermore, polymorphisms within the tribbles family genes are strongly associated with genetic susceptibility to CVDs, thereby influencing disease risk and clinical manifestations. Multiple therapeutic strategies targeting the tribbles family have demonstrated potential in improving cardiac and vascular function, offering novel avenues for CVD treatment. This review provides an in-depth analysis of the structural characteristics of tribbles family proteins and elucidates the mechanisms of tribbles in CVDs and their potential as therapeutic targets.