Molecular Regulators of Right Ventricular Angiogenesis in a Murine Model of Chronic Hypoxic Pulmonary Hypertension — Presentation Detail — Celebration of Scholars

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More information is available at carthage.edu/celebration-scholars/. The following are members of the Research, Scholarship, and Creativity Committee who are eager to listen to ideas and answer questions:

Jun Wang
Kim Instenes
John Kirk
Nora Nickels
Andrew Pustina
James Ripley

Molecular Regulators of Right Ventricular Angiogenesis in a Murine Model of Chronic Hypoxic Pulmonary Hypertension

Name: Jacelyn Peabody
Major: Biology, Neuroscience
Hometown: Colorado Springs, CO
Faculty Sponsor:
Other Sponsors: Todd Kolb MD PhD- Johns Hopkins
Type of research: Independent research
Funding: Johns Hopkins Summer Internship Program: American Heart Association Grant #13FTF17220008

Abstract

Introduction: Pulmonary hypertension (PH) is a progressive syndrome that leads to right heart failure. Increased right ventricular (RV) wall stress is mitigated through adaptive remodeling in PH. RV angiogenesis is an early component of adaptive remodeling in a mouse model of chronic hypoxic PH (CH-PH). The molecular regulators of RV angiogenesis are unknown.

Methods: Stereology was used to assess coordination of hypertrophy and angiogenesis in murine hearts to determine temporal occurrence of physiological versus pathological remodeling. Western blotting and quantitative RT-PCR were used to compare myocardial expression of regulators in mice with and without CH-PH. Microarray analysis was utilized to assess expression of tissue hypoxia-dependent genes.

Results: The temporal occurrence of RV angiogenesis and hypertrophy in murine models of CH-PH was determined to be 1-week for physiological remodeling and 3-weeks for pathological remodeling. RV angiogenesis was not associated with increased expression of VEGF protein or RNA. RV Col18A1 gene expression and endostatin protein was significantly increased after one week of CH-PH. Microarray analysis showed minimal change in hypoxia-induced gene expression during adaptive RV remodeling in CH-PH mice.

Conclusions: Early adaptive RV angiogenesis was not associated with tissue hypoxia or VEGF up-regulation, suggesting other stimuli/growth factors may be more important in this model. We hypothesize that the observed early increases in RV endostatin/Col18A1 expression may support a role in regulating angiogenesis through negative feedback.

Poster file