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Updated: Jun 8, 2026
Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
Does atorvastatin induce aortic smooth muscle cell apoptosis in vivo?
Marielle Doyon1, Taben Mary Hale, Julie-Emilie Huot-Marchand
1Faculty of Pharmacy, Université de Montréal, 2900 Édouard-Montpetit, Room 3201, P.O. Box 6128, Station Centre-Ville, Montréal, Québec, Canada, H3C 3J7. marielle.doyon@umontreal.ca
Abstract:
It has been reported that HMG-CoA reductase inhibitors such as atorvastatin induce vascular smooth muscle cell (SMC) apoptosis in vitro. However, this effect remains to be demonstrated in vivo. The present studies were designed to test the ability of atorvastatin to induce SMC apoptosis in vivo, using the spontaneously hypertensive rat (SHR) as a well-known reference model of SMC apoptosis induction in vivo by cardiovascular drugs including the calcium channel blocker amlodipine. Atorvastatin was administered to SHR for 3 or 6 weeks either alone or together with amlodipine, a drug combination clinically available to patients. Primary endpoints included aortic medial hypertrophy and aortic SMC hyperplasia, internucleosomal DNA fragmentation and expression of the apoptosis regulatory proteins Bax and Bcl-2. The SHR aorta showed no evidence of SMC apoptosis induction by atorvastatin, even at the high dose of 50 mg kg(-1) day(-1), although the statin significantly reduced oxidative stress after 3 weeks and blood pressure after 6 weeks of administration. Amlodipine-induced regression of aortic hypertophy and aortic SMC hyperplasia were dose- and time-dependent, but there was no interaction between atorvastatin and amlodipine in modulating the primary endpoints. These results do not support the notion that atorvastatin induces SMC apoptosis in the aortic media in vivo.
Insights
This study investigated atorvastatin
Area of Science:
- Cardiovascular Pharmacology
- Cellular Biology
- Pharmacology
Background:
- HMG-CoA reductase inhibitors (statins) like atorvastatin are known to induce vascular smooth muscle cell (SMC) apoptosis in vitro.
- In vivo evidence for atorvastatin-induced SMC apoptosis is lacking.
- The spontaneously hypertensive rat (SHR) model is established for in vivo studies of SMC apoptosis.
Purpose of the Study:
- To determine if atorvastatin induces SMC apoptosis in vivo.
- To investigate the interaction between atorvastatin and amlodipine on SMC apoptosis and aortic remodeling.
Main Methods:
- Administration of atorvastatin (alone or with amlodipine) to spontaneously hypertensive rats (SHR) for 3 or 6 weeks.
- Assessment of aortic medial hypertrophy, SMC hyperplasia, DNA fragmentation, and apoptosis regulatory proteins (Bax, Bcl-2).
- Measurement of oxidative stress and blood pressure.
Main Results:
- Atorvastatin did not induce SMC apoptosis in the SHR aorta, even at high doses.
- Atorvastatin reduced oxidative stress and blood pressure in SHR.
- Amlodipine induced dose- and time-dependent regression of aortic hypertrophy and SMC hyperplasia without interaction with atorvastatin.
Conclusions:
- Atorvastatin does not appear to induce vascular smooth muscle cell apoptosis in vivo.
- The combination of atorvastatin and amlodipine did not alter the effects of amlodipine alone on aortic remodeling.
- These findings do not support the hypothesis of atorvastatin-induced SMC apoptosis in the aortic media in vivo.
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