Journal article
mTORC1 (Mechanistic Target of Rapamycin Complex 1) Signaling in Endothelial and Smooth Muscle Cells Is Required for Vascular Function
Hypertension (Dallas, Tex. 1979), Vol.77(2), pp.594-604
02/01/2021
DOI: 10.1161/HYPERTENSIONAHA.120.14708
PMCID: PMC8678954
PMID: 33356400
Abstract
mTORC1 (Mechanistic target of rapamycin complex 1) serves as a molecular hub and intracellular energy sensor that regulate various cellular processes. Emerging evidence points to mTORC1 signaling as a critical regulator of cardiovascular function with implications for cardiovascular disease. Here, we show that selective disruption of mTORC1, through conditional Raptor gene deletion, in endothelial or smooth muscle cells alter vascular function. Endothelial cell-specific Raptor deletion results in reduced relaxation responses evoked by acetylcholine in the aorta but not in the mesenteric artery. Of note, endothelial-specific Raptor deletion did not affect endothelial-independent vasorelaxation nor the contractile responses of the aorta or mesenteric artery. Interestingly, endothelial Raptor haploinsufficiency did not alter vascular endothelial function but attenuated the endothelial dysfunction evoked by angiotensin II. Smooth muscle cell-specific conditional deletion of Raptor reduces both endothelial- and smooth muscle-dependent relaxation responses as well as receptor-dependent and -independent contractility in the aorta. This was associated with activation of autophagy signaling. Notably, the changes in vascular function evoked by endothelial and smooth muscle Raptor deletion were independent of changes in blood pressure and heart rate. Together, these data suggest that vascular mTORC1 signaling is a critical regulator of vascular endothelial and smooth muscle function. mTORC1 signaling may represent a potential target for the treatment of vascular diseases associated with altered mTORC1 activity.
Details
- Title: Subtitle
- mTORC1 (Mechanistic Target of Rapamycin Complex 1) Signaling in Endothelial and Smooth Muscle Cells Is Required for Vascular Function
- Creators
- John J Reho - University of Iowa, Neuroscience and PharmacologyDeng-Fu Guo - University of Iowa, Neuroscience and PharmacologyDonald A Morgan - University of Iowa, Neuroscience and PharmacologyKamal Rahmouni - University of Iowa, Neuroscience and Pharmacology
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.77(2), pp.594-604
- DOI
- 10.1161/HYPERTENSIONAHA.120.14708
- PMID
- 33356400
- PMCID
- PMC8678954
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 02/01/2021
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070462602771
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