High-mobility group box 1 serves as an inflammation driver of cardiovascular disease.

Cardiovascular disease (CVD) is the most deadly disease, which can cause sudden death, in which inflammation is a key factor in its occurrence and development. High-mobility group box 1 (HMGB1) is a novel nuclear DNA-binding protein that activates innate immunity to induce inflammation in CVD. HMGB1 exists in the cytoplasm and nucleus of different cell types, including those in the heart. By binding to its receptors, HMGB1 triggers a variety of signaling cascades, leading to inflammation and CVD. To help develop HMGB1-targeted therapies, here we discuss HMGB1 and its biological functions, receptors, signaling pathways, and pathophysiology related to inflammation and CVD, including cardiac remodeling, cardiac hypertrophy, myocardial infarction, heart failure, pulmonary hypertension, atherosclerosis, and cardiomyopathy.