ArticleAmerican journal of physiology. Heart and circulatory physiology2015
Hypertension overrides the protective effect of female hormones on the development of aortic aneurysm secondary to Alk5 deficiency via ERK activation.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Preclinical modeling of Loeys-Dietz syndrome: insights into mechanisms and therapy.Orphanet journal of rare diseases · 2026Review
- GSDMD Deficiency Attenuates the Development of Ascending Aortic Dissections in a Novel Mouse Model.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Short-term disruption of TGF-β signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection.JCI insight · 2025Article
- Second Heart Field-Derived Cells Contribute to Angiotensin II-Mediated Ascending Aortopathies.Circulation · 2022Article
- Latent TGFβ-binding proteins 1 and 3 protect the larval zebrafish outflow tract from aneurysmal dilatation.Disease models & mechanisms · 2022Article
- Nicotine Exacerbates TAAD Formation Induced by Smooth Muscle-Specific Deletion of the TGF-Journal of immunology research · 2021Article
- A validated mouse model capable of recapitulating the protective effects of female sex hormones on ascending aortic aneurysms and dissections (AADs).Physiological reports · 2020Article
- A seX(X/Y) Article on Marfan Syndrome.Journal of the American Heart Association · 2020Article
- The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the expression of the TGFβ receptor ALK5 in aorta remodeling.Molecular medicine reports · 2020Article
- Cyclophilin A contributes to aortopathy induced by postnatal loss of smooth muscle TGFBR1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Heterogeneity of Aortic Smooth Muscle Cells: A Determinant for Regional Characteristics of Thoracic Aortic Aneurysms?Journal of translational internal medicine · 2018Article
- An X-linked Myh11-CreERGenesis (New York, N.Y. : 2000) · 2017Article
- Sex, pregnancy and aortic disease in Marfan syndrome.PloS one · 2017Article
- Smooth muscle cell-specific Tgfbr1 deficiency attenuates neointimal hyperplasia but promotes an undesired vascular phenotype for injured arteries.Physiological reports · 2016Article
- Smooth muscle cell-specific Tgfbr1 deficiency promotes aortic aneurysm formation by stimulating multiple signaling events.Scientific reports · 2016Article
- Outcome Prediction Following Peritonitis Secondary to Perforated Peptic Ulcer: A Comparison of the Jabalpur Prognostic Scoring System with Mannheim Peritonitis Index in Irrua Specialist Teaching Hospital, Nigeria.Journal of the West African College of SurgeonsArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The prevalence of aortic aneurysm is five times higher in men than women among the general population. Similar sexual dimorphism also exists in syndromic aortic aneurysms triggered by TGF-β signaling disorders. To understand the responsible mechanisms, we developed an animal model where inducible deletion of the type I TGF-β receptor, Alk5, specifically in smooth muscle cells (Alk5iko) causes spontaneous aortic aneurysm formation. This model recapitulated an extreme scenario of the dimorphism in aortic aneurysm development between genders. In a comparative experiment, all Alk5iko males (n=42) developed aortic aneurysms and 26% of them died prematurely from aortic rupture. In contrast, the Alk5iko females (n=14) presented only a subclinical phenotype characteristic of scarcely scattered elastin breaks. Removal of male hormones via orchiectomy (n=7) resulted in only minimal influence on aortic pathology. However, reduction of female hormones via ovariectomy (n=15) increased the phenotypic penetrance from zero to 53%. Finally, an elevation of systolic blood pressure by 30 points unmasked the subclinical phenotype of Alk5iko females (n=17) to 59%. This exaggerated phenotypic penetrance was coupled with an early intensification of ERK signaling, a molecular signature that correlated to 100% phenotypic penetrance in normotensive Alk5iko males. In conclusion, aortic aneurysm induced by Alk5iko exhibits dimorphic incidence between genders with females less susceptible to aortic disease. This sexual dimorphism is partially the result from the protective effects of female hormones. Hypertension, a known risk factor for aortic aneurysm, is able to break the female sex protective effects through mechanisms associated with enhanced ERK activity.
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