Related Experiment Video
Updated: Aug 5, 2026
05:31
Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
Chemogenetic Ca2+ Channel Mitigates Aortic Dissection and Antihypertensive Risk
Xuan Wang1, Xiao-Tian Li1, Hao-Nan Chen1
1Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, China (X.W., X.-T.L., H.-N.C., H.-L.Z., J.K., Y.-N.H., J.-F.P., C.-P.H., Z.Z.).
Hypertension (Dallas, Tex. : 1979)
|August 3, 2026
Summary
Certain blood pressure drugs like hydrochlorothiazide and minoxidil may worsen thoracic aortic dissection (TAD). A novel chemogenetic therapy targeting calcium signaling shows promise for treating TAD and counteracting harmful drug effects.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Thoracic aortic dissection (TAD) is a life-threatening condition lacking effective drug treatments.
- Current guidelines emphasize controlling hypertension, but no trials have guided antihypertensive selection for TAD.
- Diverse antihypertensive mechanisms exist, necessitating research into their efficacy and safety in TAD.
Purpose of the Study:
- To evaluate the efficacy and safety of various antihypertensive drug classes in a mouse model of TAD.
- To investigate the underlying mechanisms of TAD pathogenesis and drug-induced exacerbation.
- To explore novel therapeutic strategies targeting smooth muscle cell calcium signaling for TAD.
Main Methods:
- Assessment of 8 antihypertensive classes in a 3-aminopropionitrile-induced mouse TAD model.
- Pharmacovigilance analysis using FDA Adverse Events Reporting System and MIMIC databases.
- Meta-analysis of 32 studies, examination of signaling pathways, and generation of a chemogenetic mouse model.
Main Results:
- Hydrochlorothiazide and minoxidil unexpectedly exacerbated TAD in the mouse model.
- Diuretic use was linked to increased TAD risk in patient pharmacovigilance data.
- A chemogenetic actuator (PSAM4-5-HT3R) enhanced smooth muscle cell Ca2+ signaling, protecting against TAD.
Conclusions:
- Certain antihypertensives require pharmacovigilance in TAD patients.
- Targeting Ca2+ signaling via chemogenetics offers a potential therapeutic avenue for TAD.
- The PSAM4-5-HT3R system demonstrates translational potential for managing thoracic aortic dissection.
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