Potential Roles of Metals in the Pathogenesis of Pulmonary and Systemic Hypertension

C. Danielle Hopkins, Caitlin Wessel, Oscar Chen, Karim El-Kersh, Matthew C. Cave, Lu Cai, Jiapeng Huang

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Pulmonary and systemic hypertension (PH, SH) are characterized by vasoconstriction and vascular remodeling resulting in increased vascular resistance and pulmonary/aortic artery pressures. The chronic stress leads to inflammation, oxidative stress, and infiltration by immune cells. Roles of metals in these diseases, particularly PH are largely unknown. This review first discusses the pathophysiology of PH including vascular oxidative stress, inflammation, and remodeling in PH; mitochondrial dysfunction and metabolic changes in PH; ion channel and its alterations in the pathogenesis of PH as well as PH-associated right ventricular (RV) remodeling and dysfunctions. This review then summarizes metal general features and essentiality for the cardiovascular system and effects of metals on systemic blood pressure. Lastly, this review explores non-essential and essential metals and potential roles of their dyshomeostasis in PH and RV dysfunction. Although it remains early to conclude the role of metals in the pathogenesis of PH, emerging direct and indirect evidence implicates the possible contributions of metal-mediated toxicities in the development of PH. Future research should focus on comprehensive clinical metallomics study in PH patients; mechanistic evaluations to elucidate roles of various metals in PH animal models; and novel therapy clinical trials targeting metals. These important discoveries will significantly advance our understandings of this rare yet fatal disease, PH.

Original languageEnglish (US)
Pages (from-to)5036-5054
Number of pages19
JournalInternational Journal of Biological Sciences
Volume19
Issue number16
DOIs
StatePublished - 2023

Keywords

  • Heavy metals
  • Hypertension
  • Mineral homeostasis
  • Mitochondrial dysfunction
  • Non-essential metals
  • Pulmonary artery hypertension
  • Pulmonary hypoxia
  • Right ventricle dysfunction
  • Trace elements

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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