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Updated: Jan 23, 2026

Vascular Balloon Injury and Intraluminal Administration in Rat Carotid Artery
Published on: December 23, 2014
Transmembrane protein 66 attenuates neointimal hyperplasia after carotid artery injury by SOCE inactivation
Jiong Yang1, Shuang Li1, Qiang Wang1
1Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China.
Abstract:
Neointimal hyperplasia could be one of the most important complications after balloon angioplasty. Since calcium signaling has several physiologic effects on the regulation of the proliferation and migration of vascular smooth muscle cells (VSMCs), it was hypothesized that transmembrane protein 66 (TMEM66), a store operated calcium entry (SOCE)‑associated regulatory factor, possesses vascular protection against balloon injury. The rat balloon‑induced carotid artery injury model was performed. Histological analysis was used to check neointimal hyperplasia. TMEM66 expression was measured by PCR and immunoblotting. The results revealed that TMEM66 was expressed in the medial and neointimal layers of the injured artery, and the expression of TMEM66 was markedly decreased. TMEM66 overexpression attenuated neointimal hyperplasia via VSMC proliferation/migration inhibition, and restored expression of VSMC phenotypic markers. Moreover, TMEM66 overexpression reduced the increased expression of Stim1 and Orai1 and PDGF‑BB treatment‑enhanced [Ca2+]i. In conclusion, TMEM66 protects against balloon injury‑induced neointimal hyperplasia, and may be a pharmacological target for the treatment of restenosis.
Insights
Transmembrane protein 66 (TMEM66) protects against neointimal hyperplasia after balloon angioplasty. Overexpression of TMEM66 inhibits vascular smooth muscle cell proliferation and migration, offering potential for restenosis treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Biology
Background:
- Neointimal hyperplasia is a major complication following balloon angioplasty.
- Calcium signaling regulates vascular smooth muscle cell (VSMC) proliferation and migration.
- Transmembrane protein 66 (TMEM66) is associated with store-operated calcium entry (SOCE).
Purpose of the Study:
- To investigate the role of TMEM66 in vascular protection against balloon injury.
- To determine if TMEM66 expression is altered after arterial injury.
- To explore the therapeutic potential of TMEM66 in preventing neointimal hyperplasia.
Main Methods:
- Rat balloon-induced carotid artery injury model.
- Histological analysis for neointimal hyperplasia assessment.
- Quantitative PCR and immunoblotting for TMEM66 expression analysis.
- Assessment of VSMC proliferation, migration, and phenotypic markers.
- Measurement of intracellular calcium levels ([Ca2+]i).
Main Results:
- TMEM66 expression was decreased in injured rat carotid arteries.
- TMEM66 overexpression attenuated neointimal hyperplasia.
- TMEM66 overexpression inhibited VSMC proliferation and migration, restoring VSMC phenotypic markers.
- TMEM66 overexpression reduced Stim1 and Orai1 expression and PDGF-BB-induced intracellular calcium increase.
Conclusions:
- TMEM66 plays a protective role against balloon injury-induced neointimal hyperplasia.
- TMEM66 modulates calcium signaling pathways involved in VSMC behavior.
- TMEM66 represents a potential pharmacological target for treating restenosis.
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