Browsing by Subject "Pulmonary vascular remodeling"

Now showing 1 - 3 of 3
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    Editorial: Pathophysiology and Pathogenic Mechanisms of Pulmonary Vascular Disease
    (Frontiers Media, 2022-03-18) Zhu, Jinsheng; Chen, Jiwang; Wang, Jian; Desai, Ankit A.; Black, Stephen M.; Tang, Haiyang; Medicine, School of Medicine
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    New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis
    (American Heart Association, 2022) Aldred, Micheala A.; Morrell, Nicholas W.; Guignabert, Christophe; Medicine, School of Medicine
    Pulmonary arterial hypertension (PAH) is a complex multifactorial disease with poor prognosis characterized by functional and structural alterations of the pulmonary circulation causing marked increase in pulmonary vascular resistance (PVR), ultimately leading to right heart failure and death. Mutations in the gene encoding Bone Morphogenetic Protein Receptor type 2 (BMPR2), a receptor for the transforming growth factor-beta (TGF-β) superfamily, account for over 70% of families with PAH, and approximately 20% of sporadic cases. In recent years, however, less common or rare mutations in other genes have been identified. This review will consider how these newly discovered PAH genes could help to provide a better understanding of the molecular and cellular bases of the maintenance of the pulmonary vascular integrity, as well as their role in the PAH pathogenesis underlying occlusion of arterioles in the lung. We will also discuss how insights into the genetic contributions of these new PAH-related genes may open up new therapeutic targets for this, currently incurable, cardiopulmonary disorder.
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    Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function
    (American Physiological Society, 2019-02-15) Philip, Jennifer L.; Murphy, Thomas M.; Schreier, David A.; Stevens, Sydney; Tabima, Diana M.; Albrecht, Margie; Frump, Andrea L.; Hacker, Timothy A.; Lahm, Tim; Chesler, Naomi C.; Medicine, School of Medicine
    Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate mechanical mechanisms of pulmonary vascular and RV dysfunction in a rodent model of LHF to address the knowledge gaps in understanding disease pathophysiology. LHF was created using a left anterior descending artery ligation to cause myocardial infarction (MI) in mice. Sham animals underwent thoracotomy alone. Echocardiography demonstrated increased left ventricle (LV) volumes and decreased ejection fraction at 4 wk post-MI that did not normalize by 12 wk post-MI. Elevation of LV diastolic pressure and RV systolic pressure at 12 wk post-MI demonstrated pulmonary hypertension (PH) due to LHF. There was increased pulmonary arterial elastance and pulmonary vascular resistance associated with perivascular fibrosis without other remodeling. There was also RV contractile dysfunction with a 35% decrease in RV end-systolic elastance and 66% decrease in ventricular-vascular coupling. In this model of PH due to LHF with reduced ejection fraction, pulmonary fibrosis contributes to increased RV afterload, and loss of RV contractility contributes to RV dysfunction. These are key pathologic features of human PH secondary to LHF. In the future, novel therapeutic strategies aimed at preventing pulmonary vascular mechanical changes and RV dysfunction in the context of LHF can be tested using this model.