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Yet, the common experimental model of angiotensin II-induced aortopathy in mice appears independent of high blood pressure as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by co-treatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice 1 week after disruption of TGF\u03b2 signaling in smooth muscle cells. Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes that was rescued by hydralazine; results were similar with angiotensin II. Changes in regulatory contractile molecule expression were not of pathological significance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically type XVIII, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure cause dissection in aortas rendered vulnerable by inhibition of TGF\u03b2-driven extracellular matrix production by smooth muscle cells. A corollary is that medial fibrosis, a frequent feature of medial degeneration, may afford some protection against aortic dissection.<\/jats:p>","DOI":"10.1101\/2024.04.22.590484","type":"posted-content","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:13Z","timestamp":1714176013000},"source":"Crossref","is-referenced-by-count":1,"title":["Short-Term Disruption of TGF\u03b2 Signaling in Adult Mice Renders the Aorta Vulnerable to Hypertension-Induced 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