2024
Endothelial HIFα-PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension
Saddouk F, Kuzemczak A, Saito J, Greif D. Endothelial HIFα-PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension. JCI Insight 2024, 9: e162449. PMID: 38652543, PMCID: PMC11141934, DOI: 10.1172/jci.insight.162449.Peer-Reviewed Original ResearchSmooth muscle cellsArteriole smooth muscle cellsPulmonary hypertensionPlatelet-derived growth factor-BDistal muscularizationSugen 5416Endothelial cellsHuman idiopathic pulmonary arterial hypertensionHypoxia-induced pulmonary vascular remodelingPulmonary artery smooth muscle cellsIdiopathic pulmonary arterial hypertensionHypoxia-inducible factor (HIF)-1aArtery smooth muscle cellsDistal pulmonary arteriolesPulmonary arterial hypertensionPulmonary vascular remodelingDeletion of Hif1aLung endothelial cellsGrowth factor BEC-specific deletionPulmonary arteriolesArterial hypertensionLung lysatesMuscle cellsVascular remodeling
2021
Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension
Ntokou A, Dave JM, Kauffman AC, Sauler M, Ryu C, Hwa J, Herzog EL, Singh I, Saltzman WM, Greif DM. Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension. JCI Insight 2021, 6: e139067. PMID: 33591958, PMCID: PMC8026182, DOI: 10.1172/jci.insight.139067.Peer-Reviewed Original ResearchConceptsRight ventricle hypertrophyPulmonary hypertensionDistal muscularizationSmooth muscle cellsHypoxia-inducible factor 2APulmonary arterial hypertension patientsLysM-Cre miceArterial hypertension patientsHuman pulmonary hypertensionHypoxia-inducible factor 1aPlatelet-derived growth factorMacrophage-conditioned mediumVentricle hypertrophyHypertension patientsDistal arteriolesMacrophage accumulationFl miceCardiovascular diseaseInterventional strategiesMuscularizationHypoxia exposureExcess macrophagesSMC proliferationLethal diseaseMuscle cells