The roles of neutrophils in cardiovascular diseases

Abstract

The immune response plays a vital role in the development of cardiovascular diseases (CVDs). As a crucial component of the innate immune system, neutrophils are involved in the initial inflammatory response following cardiovascular injury, thereby inducing subsequent damage and promoting recovery. Neutrophils exert their functional effects in tissues through various mechanisms, including activation and the formation of neutrophil extracellular traps (NETs). Once activated, neutrophils are recruited to the site of injury, where they release inflammatory mediators and cytokines. This study discusses the main mechanisms associated with neutrophil activity and proposes potential new therapeutic targets. In this review, we systematically summarize the diverse phenotypes of neutrophils in disease regulatory mechanisms, different modes of cell death, and focus on the relevance of neutrophils to various CVDs, including atherosclerosis, acute coronary syndrome, myocardial ischemia/reperfusion injury, hypertension, atrial fibrillation, heart failure, and viral myocarditis. Finally, we also emphasize the preclinical/clinical translational significance of neutrophil-targeted strategies.

Keywords: cardiovascular diseases; inflammation; innate immunology; neutrophil extracellular traps (NETs); neutrophils.

Figure 1

Partial markers of neutrophils. illustrates the heterogeneity of neutrophils in different states, including the markers of immature, mature, and activated neutrophils in the bone marrow (A), the markers of positive migration and aging in the bloodstream (B), and the markers of migration to various tissues and organs in the human body (C) (Created using Figdraw).

Figure 2

Mechanisms of neutrophil death. provides an overview of the four common modes of neutrophil death: apoptosis, NETosis, pyroptosis, and ferroptosis. At sites of cardiac injury, neutrophil death can be triggered by a variety of factors, including pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), bacteria, and viruses. Different modes of death can be induced through distinct pathways and are interrelated (Created using Figdraw).

Figure 3

Neutrophils and cardiovascular diseases. Illustrates the complex relationship between neutrophils and cardiovascular diseases. Neutrophils play a pivotal role in the pathogenesis of various cardiovascular conditions, including atherosclerosis, myocardial infarction, and heart failure. They contribute to inflammation, plaque formation, and tissue damage through the release of pro-inflammatory cytokines, reactive oxygen species, and proteolytic enzymes.