cAMP enriched EVs mediates hypoxic pulmonary hypertension

• DOI: 10.1152/physiol.2024.39.s1.714
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Aritra Bhadra; Jenny Hewes; Ji Young Lee; Chun Zhou; Frederic Bonnie; Natalie Bauer
• Keywords: Hypoxia

Our lab reported the novel finding that stimulation of pulmonary endothelial cells with a beta-agonist and phosphodiesterase inhibitor induced enrichment cyclic adenosine monophosphate (cAMP) in EVs. cAMP protects vasculature by regulation permeability, vasoreactivity proliferation. Extracellular vesicles provide protected environment for circulating cAMP. Thus, we hypothesized administration cAMP, an EV, could deliver to improve outcomes hypertension. Briefly, male Sprague Dawley rats, maintained normoxic or hypoxic conditions 3 weeks, received 50 ug cAMP-enriched EVs (cAMP-EVs) per day over days via tail vein injection. cAMP-EV injections improved Fulton index (non-injected hypoxia rat 0.37 ± 0.039 versus injected 0.32 0.019, p value 0.032 n = 5) echocardiography revealed PH rats cAMP-EVs had significant increase PAAT/PAET ratio compared those did not 0.27 0.056 0.04, 6). Using IVIS analysis isolated tissues detect PKH-labeled found accumulated lung but were detectable heart. To confirm this was strictly effect, also examined PCNA, marker proliferation, histological sections it decreased presence cAMP-EVs. Pulmonary arterial thickness significantly understand underlying mechanism based signaling, studied phosphorylation status nitric oxide synthase (eNOS) paraffn fixed slices. We increased eNOS which non-injected control rats. Combined these data suggest may decrease right ventricular hypertrophy, function, repair vascular injury. Future investigations will determine whether observed response is dependent further evaluate specificity uptake 1R01HL133066-01A1 (Bauer). This full abstract presented at American Physiology Summit 2024 meeting only available HTML format. There are no additional versions content abstract. involved peer review process.