2022
DOI: 10.1101/2022.07.21.501037
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Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Abstract: Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic (ATA) compared to distal segments of the aorta and that tissues in both the medial and adventitial compartments of the ATA stiffen during aging. Single-cell RNA sequ… Show more

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Cited by 3 publications
(5 citation statements)
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“…5 ). These estimates are in close agreement with experimental ( 33 , 39 , 40 ) and theoretical ( 38 ) values from literature. All 12-week-old Hspg2 specimens fell within the 95% confidence interval for the expected ATA diameter by body mass ( Figure 1G ).…”
Section: Resultssupporting
confidence: 91%
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“…5 ). These estimates are in close agreement with experimental ( 33 , 39 , 40 ) and theoretical ( 38 ) values from literature. All 12-week-old Hspg2 specimens fell within the 95% confidence interval for the expected ATA diameter by body mass ( Figure 1G ).…”
Section: Resultssupporting
confidence: 91%
“…All biomechanical testing and data analysis was performed consistent with established methods ( 12 , 32 , 33 , 34 ). The thoracic aorta was cleaned of excess fat and perivascular tissues, while preserving lateral branches.…”
Section: Methodsmentioning
confidence: 99%
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“…Whole aortas were immediately excised, immersed in chilled (4 ◦ C) Hank’s buffered salt solution (HBSS), and prepared for mechanical testing as previously described. 31, 34 Briefly, the ascending thoracic aorta (ATA) was sectioned between the aortic root and the brachiocephalic artery, while the suprarenal abdominal aorta (SAA) was segmented from the diaphragm to the right renal artery. Aortic samples were cleaned of perivascular tissue to facilitate ligation of lateral branches using a single strand of a braided 9-0 suture.…”
Section: Methodsmentioning
confidence: 99%
“…The activation of Cdc42 by protein kinase C delta type initiates the production of type I collagen from vascular smooth muscle cells [221]. Aging increases Cdc42 signaling in VSMC [223], potentially increasing collagen I secretion and leading to vascular fibrosis and atherosclerosis complications [224]. Moreover, overexpression of Cdc42 may increase arterial stiffness due to enhanced osteogenic differentiation of VSMC and subsequent vascular calcification [225].…”
Section: Cdc42 Obesity and Agingmentioning
confidence: 99%