The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype

Olga Rafikova, Ruslan Rafikov, Mary Louise Meadows, Archana Kangath, Danny Jonigk, Stephen Matthew Black

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Although female predominance in the development of all types of pulmonary hypertension (PH) is well established, many clinical studies have confirmed that females have better prognosis and higher survival rate than males. There is no clear explanation of why sex influences the pathogenesis and progression of PH. Using a rat angioproliferative model of PH, which closely resembles the primary pathological changes observed in humans, we evaluated the role of sex in the development and progression of PH. Female rats had a more pronounced increase in medial thickness in the small pulmonary arteries. However, the infiltration of small pulmonary arteries by inflammatory cells was found only in male rats, and this corresponded to increased myeloperoxidase activity and abundant adventitial and medial fibrosis that were not present in female rats. Although the level of right ventricle (RV) peak systolic pressure was similar in both groups, the survival rate in male rats was significantly lower. Moreover, male rats presented with a more pronounced increase in RV thickness that correlated with diffuse RV fibrosis and significantly impaired right cardiac function. The reduction in fibrosis in female rats correlated with increased expression of caveolin-1 and reduced endothelial nitric oxide synthase–derived superoxide. We conclude that, in the pathogenesis of PH, female sex is associated with greater remodeling of the pulmonary arteries but greater survival. Conversely, in males, the development of pulmonary and cardiac fibrosis leads to early and severe RV failure, and this may be an important reason for the lower survival rate among males.

Original languageEnglish (US)
Pages (from-to)184-197
Number of pages14
JournalPulmonary Circulation
Volume5
Issue number1
DOIs
StatePublished - Mar 1 2015

Fingerprint

Pulmonary Hypertension
Sex Characteristics
Phenotype
Heart Ventricles
Pulmonary Artery
Fibrosis
Caveolin 1
Adventitia
Sexual Development
Pulmonary Fibrosis
Superoxides
Peroxidase
Nitric Oxide
Blood Pressure
Survival

Keywords

  • Caveolin-1
  • Nitric oxide synthase
  • Oxidative stress
  • Superoxide

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Rafikova, O., Rafikov, R., Meadows, M. L., Kangath, A., Jonigk, D., & Black, S. M. (2015). The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype. Pulmonary Circulation, 5(1), 184-197. https://doi.org/10.1086/679724

The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype. / Rafikova, Olga; Rafikov, Ruslan; Meadows, Mary Louise; Kangath, Archana; Jonigk, Danny; Black, Stephen Matthew.

In: Pulmonary Circulation, Vol. 5, No. 1, 01.03.2015, p. 184-197.

Research output: Contribution to journalArticle

Rafikova, O, Rafikov, R, Meadows, ML, Kangath, A, Jonigk, D & Black, SM 2015, 'The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype', Pulmonary Circulation, vol. 5, no. 1, pp. 184-197. https://doi.org/10.1086/679724
Rafikova, Olga ; Rafikov, Ruslan ; Meadows, Mary Louise ; Kangath, Archana ; Jonigk, Danny ; Black, Stephen Matthew. / The sexual dimorphism associated with pulmonary hypertension corresponds to a fibrotic phenotype. In: Pulmonary Circulation. 2015 ; Vol. 5, No. 1. pp. 184-197.
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