Pulmonary vascular and ventricular dysfunction in the susceptible patient (2015 grover conference series)

Bradley A. Maron, Roberto Machado, Larissa Shimoda

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Pulmonary blood vessel structure and tone are maintained by a complex interplay between endogenous vasoactive factors and oxygen-sensing intermediaries. Under physiological conditions, these signaling networks function as an adaptive interface between the pulmonary circulation and environmental or acquired perturbations to preserve oxygenation and maintain systemic delivery of oxygen-rich hemoglobin. Chronic exposure to hypoxia, however, triggers a range of pathogenetic mechanisms that include hypoxia-inducible factor 1α (HIF-1α)–dependent upregulation of the vasoconstrictor peptide endothelin 1 in pulmonary endothelial cells. In pulmonary arterial smooth muscle cells, chronic hypoxia induces HIF-1α-mediated upregulation of canonical transient receptor potential proteins, as well as increased Rho kinase-Ca2+ signaling and pulmonary arteriole synthesis of the profibrotic hormone aldosterone. Collectively, these mechanisms contribute to a contractile or hypertrophic pulmonary vascular phenotype. Genetically inherited disorders in hemoglobin structure are also an important etiology of abnormal pulmonary vasoreactivity. In sickle cell anemia, for example, consumption of the vasodilator and antimitogenic molecule nitric oxide by cell-free hemoglobin is an important mechanism underpinning pulmonary hypertension. Contemporary genomic and transcriptomic analytic methods have also allowed for the discovery of novel risk factors relevant to sickle cell disease, including GALNT13 gene variants. In this report, we review cutting-edge observations characterizing these and other pathobiological mechanisms that contribute to pulmonary vascular and right ventricular vulnerability.

Original languageEnglish (US)
Pages (from-to)426-438
Number of pages13
JournalPulmonary Circulation
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Ventricular Dysfunction
Blood Vessels
Lung
Hypoxia-Inducible Factor 1
Hemoglobins
Sickle Cell Anemia
Up-Regulation
Oxygen
Cell Hypoxia
rho-Associated Kinases
Pulmonary Circulation
Arterioles
Vasoconstrictor Agents
Endothelin-1
Aldosterone
Vasodilator Agents
Pulmonary Hypertension
Smooth Muscle Myocytes
Nitric Oxide
Endothelial Cells

Keywords

  • Genetics
  • Hypoxia
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Pulmonary vascular and ventricular dysfunction in the susceptible patient (2015 grover conference series). / Maron, Bradley A.; Machado, Roberto; Shimoda, Larissa.

In: Pulmonary Circulation, Vol. 6, No. 4, 01.01.2018, p. 426-438.

Research output: Contribution to journalReview article

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