Blockade of YAP Mechanoactivation Prevents Neointima Formation and Adverse Remodeling in Arterialized Vein Grafts DOI Creative Commons
Gloria Garoffolo, Thijs J. Sluiter, Anita C. Thomas

и другие.

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Background Bypass surgery using saphenous vein (SV) grafts is commonly performed to revascularize the ischemic heart and lower limbs. These interventions have limited success due adverse remodeling caused by overproliferation of smooth muscle cells in intima layer, leading progressive bypass stenosis. We previously showed that cyclic strain deriving from exposure coronary flow induces expression matricellular protein thrombospondin‐1 human SV, promoting activation progenitor normally residing adventitia. Methods analyzed data an RNA‐sequencing profiling SV progenitors subjected uniaxial we by. Experiments cell culture, ex vivo, vivo arterialization models were substantiate findings with particular reference role mechanically activated transcription factors. Validation was vitro vivo/in graft disease. Results bioinformatic assessment indicated Yes‐associated (YAP) as a possible regulated effector pathologic evolution progenitors. Inhibition YAP verteprofin—a drug abolishes interaction Tea Domain DNA–binding proteins—reduced markers reduced hyperplasia vivo. Conclusions Our results reveal desensitizing SV‐resident mechanoactivation feasible reduce disease progression.

Язык: Английский

Blockade of YAP Mechanoactivation Prevents Neointima Formation and Adverse Remodeling in Arterialized Vein Grafts DOI Creative Commons
Gloria Garoffolo, Thijs J. Sluiter, Anita C. Thomas

и другие.

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Background Bypass surgery using saphenous vein (SV) grafts is commonly performed to revascularize the ischemic heart and lower limbs. These interventions have limited success due adverse remodeling caused by overproliferation of smooth muscle cells in intima layer, leading progressive bypass stenosis. We previously showed that cyclic strain deriving from exposure coronary flow induces expression matricellular protein thrombospondin‐1 human SV, promoting activation progenitor normally residing adventitia. Methods analyzed data an RNA‐sequencing profiling SV progenitors subjected uniaxial we by. Experiments cell culture, ex vivo, vivo arterialization models were substantiate findings with particular reference role mechanically activated transcription factors. Validation was vitro vivo/in graft disease. Results bioinformatic assessment indicated Yes‐associated (YAP) as a possible regulated effector pathologic evolution progenitors. Inhibition YAP verteprofin—a drug abolishes interaction Tea Domain DNA–binding proteins—reduced markers reduced hyperplasia vivo. Conclusions Our results reveal desensitizing SV‐resident mechanoactivation feasible reduce disease progression.

Язык: Английский

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