Hypertension: Do Inflammation and Immunity Hold the Key to Solving this Epidemic?

Circ Res. 2021 Apr 2;128(7):908-933. doi: 10.1161/CIRCRESAHA.121.318052. Epub 2021 Apr 1.

Abstract

Elevated cardiovascular risk including stroke, heart failure, and heart attack is present even after normalization of blood pressure in patients with hypertension. Underlying immune cell activation is a likely culprit. Although immune cells are important for protection against invading pathogens, their chronic overactivation may lead to tissue damage and high blood pressure. Triggers that may initiate immune activation include viral infections, autoimmunity, and lifestyle factors such as excess dietary salt. These conditions activate the immune system either directly or through their impact on the gut microbiome, which ultimately produces chronic inflammation and hypertension. T cells are central to the immune responses contributing to hypertension. They are activated in part by binding specific antigens that are presented in major histocompatibility complex molecules on professional antigen-presenting cells, and they generate repertoires of rearranged T-cell receptors. Activated T cells infiltrate tissues and produce cytokines including interleukin 17A, which promote renal and vascular dysfunction and end-organ damage leading to hypertension. In this comprehensive review, we highlight environmental, genetic, and microbial associated mechanisms contributing to both innate and adaptive immune cell activation leading to hypertension. Targeting the underlying chronic immune cell activation in hypertension has the potential to mitigate the excess cardiovascular risk associated with this common and deadly disease.

Keywords: T-lymphocytes; autoimmunity; cytokines; dendritic cells; hypertension; immunity; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • B-Lymphocytes / immunology
  • Complement System Proteins / immunology
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Drug Resistance
  • Female
  • Gastrointestinal Microbiome / immunology
  • Heart Disease Risk Factors
  • Host Microbial Interactions
  • Humans
  • Hypertension / drug therapy
  • Hypertension / immunology*
  • Immune System Phenomena
  • Immunity, Cellular / physiology*
  • Immunity, Innate
  • Inflammasomes / immunology
  • Inflammation / genetics
  • Inflammation / immunology
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Male
  • Monocytes / immunology
  • Sex Factors
  • Sodium Chloride, Dietary / adverse effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Virus Diseases / immunology

Substances

  • Antihypertensive Agents
  • Cytokines
  • Inflammasomes
  • Sodium Chloride, Dietary
  • Complement System Proteins