Journal Article

Neutrophil-Initiated Myocardial Inflammation and Its Modulation by B-Type Natriuretic Peptide: A Potential Therapeutic Target

Horowitz, John D., Chirkov, Yuliy Y., Liu, Saifei

2018

Overview

Activation of neutrophils is a critically important component of the innate immune response to bacterial and chemical stimuli, and culminates in the “neutrophil burst”, which facilitates neutrophil phagocytosis via the release of superoxide anion radical (O2−) from NADPH oxidase. Excessive and/or prolonged neutrophil activation results in substantial tissue injury and increases in vascular permeability—resulting in sustained tissue infiltration with neutrophils and monocytes, and persistent vasomotor dysfunction. Cardiovascular examples of such changes include acute and chronic systolic and diastolic heart failure (“heart failure with preserved ejection fraction”), and the catecholamine-induced inflammatory disorder takotsubo syndrome. We have recently demonstrated that B-type natriuretic peptide (BNP), acting via inhibition of activation of neutrophil NADPH oxidase, is an important negative modulator of the “neutrophil burst”, though its effectiveness in limiting tissue injury is partially lost in acute heart failure. The potential therapeutic implications of these findings, regarding the development of new means of treating both acute and chronic cardiac injury states, are discussed.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Apoptosis / Cardiomyopathy / Chemokines / Cytokines / Endothelium / Enzymes / Free Radicals - metabolism / Gene expression / Heart failure / Humans / Immunologic Factors - metabolism / Immunologic Factors - therapeutic use / Inflammation / Myocardium - metabolism / Natriuretic Peptide, Brain - metabolism / Natriuretic Peptide, Brain - therapeutic use / Neutrophils / Neutrophils - metabolism / Nitric oxide / Peptides / Permeability / Pulmonary hypertension / Review / Rheology / Takotsubo Cardiomyopathy - drug therapy / Takotsubo Cardiomyopathy - metabolism