Cellular Communication Network Protein 2 in the Right Ventricle of Pulmonary Arterial Hypertension.

IF 2.2 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Carly E Byrd, Jennifer E Schramm, Jun Yang, Allan E Barnes, Megan Griffiths, Anjira S Ambade, Darin T Rosen, Ilton M Cubero Salazar, Catherine E Simpson, Ryan J Tedford, Steven Hsu, Dhananjay Vaidya, Todd M Kolb, Michael W Pauciulo, William C Nichols, David D Ivy, Eric D Austin, Paul M Hassoun, Rachel L Damico, Allen D Everett
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引用次数: 0

Abstract

Cellular communication network 2 (CCN2) is a secreted matricellular protein associated with pulmonary arterial hypertension (PAH) but has not been studied relative to PAH severity, outcomes, or right ventricle (RV) structure and function in a large human cohort and preclinical animal model. This study assessed the associations between CCN2 and PAH severity, survival, hemodynamic measurements, and cardiovascular dysfunction. Serum CCN2 levels were compared in 2548 adults with PAH and 216 controls. CCN2 levels in PAH patients were compared to functional and hemodynamic measurements, and survival outcomes. RV-pulmonary artery coupling and RV morphology were also assessed in a small subset of patients via pressure-volume loops and cardiac magnetic resonance imaging. In a preclinical PAH model, plasma CCN2 levels were compared between ventricles with PAH progression. CCN2 mRNA levels in both ventricles in the preclinical model were measured to compare with morphologic histologic variables. CCN2 serum levels were significantly higher in PAH compared to controls (p < 0.0001). Higher CCN2 levels were associated with reduced RV contractility (p = 0.003). Higher CCN2 levels were associated with worse 6MWD (p = 0.035), and higher risk of mortality or transplant (p = 0.025). In the preclinical model, prepulmonary CCN2 plasma levels increased with the progression of disease. CCN2 mRNA levels in the RV were associated with decreased RV capillary density (p = 0.015) and increased RV fibrosis (p = 0.045). Though more investigation is needed, it appears that CCN2 plays a role in the development of PAH and potentially in RV maladaptation in PAH.

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来源期刊
Pulmonary Circulation
Pulmonary Circulation Medicine-Pulmonary and Respiratory Medicine
CiteScore
4.20
自引率
11.50%
发文量
153
审稿时长
15 weeks
期刊介绍: Pulmonary Circulation''s main goal is to encourage basic, translational, and clinical research by investigators, physician-scientists, and clinicans, in the hope of increasing survival rates for pulmonary hypertension and other pulmonary vascular diseases worldwide, and developing new therapeutic approaches for the diseases. Freely available online, Pulmonary Circulation allows diverse knowledge of research, techniques, and case studies to reach a wide readership of specialists in order to improve patient care and treatment outcomes.
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