2023
A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension
Gunawardhana K, Hong L, Rugira T, Uebbing S, Kucharczak J, Mehta S, Karunamuni D, Cabera-Mendoza B, Gandotra N, Scharfe C, Polimanti R, Noonan J, Mani A. A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. Journal Of Clinical Investigation 2023, 133: e160036. PMID: 36602864, PMCID: PMC9927944, DOI: 10.1172/jci160036.Peer-Reviewed Original ResearchConceptsDevelopment of hypertensionParallel reporter assaysRenin inhibitor aliskirenNeural crest-derived cellsRenin-producing cellsSystems biology approachRNA-seq analysisCell-specific disruptionCrest-derived cellsSmooth muscle cellsMuscle cell proteinsSystemic hypertensionBlood pressureWT miceAntihypertensive drugsBiology approachSuper enhancersFine mappingWT littermatesThird intronMultiple GWASCollagen depositionMouse aortaReporter assaysFate mapping
2021
Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice
Spronck B, Latorre M, Wang M, Mehta S, Caulk AW, Ren P, Ramachandra AB, Murtada SI, Rojas A, He CS, Jiang B, Bersi MR, Tellides G, Humphrey JD. Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice. Journal Of The Royal Society Interface 2021, 18: 20210336. PMID: 34314650, PMCID: PMC8315831, DOI: 10.1098/rsif.2021.0336.Peer-Reviewed Original ResearchConceptsAortic remodellingWall stressAngiotensin II infusionInflammatory cell infiltrationC57BL/6 J miceSmooth muscle contractile processHigh wall stressVasoconstrictive capacityII infusionBlood pressureInflammatory cellsCell infiltrationMean wall stressJ miceThoracic aortaMaladaptive remodellingImmune processesAortaBulk RNA sequencingBiomechanical assessmentAdaptive remodellingContractile processMarked increaseRemodellingVasoconstriction