更高的 TIMP-1 蛋白水平和新内膜形成代表了限制雌性大鼠主动脉血管扩张的性别依赖性细胞事件

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2024-09-12 DOI:10.1002/iub.2916
Aya Al‐Katat, Laurie Boudreau, Emmanuelle Gagnon, Ines Assous, Louis Villeneuve, Charles Alexandre Leblanc, Alexandre Bergeron, Martin Sirois, Ismael El‐Hamamsy, Angelino Calderone
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引用次数: 0

摘要

结构蛋白弹性蛋白的碎裂/损失是导致主动脉扩张和随后动脉瘤形成的诱因。本研究验证了一个假设,即基质金属蛋白酶组织抑制剂-1(TIMP-1)蛋白表达量增加和内侧弹性蛋白含量减少导致的新内膜生长是限制女性主动脉血管扩张的性别依赖性事件。与男性相比,女性主动脉瓣二尖瓣(BAV)患者升主动脉中的 TIMP-1 蛋白水平更高。后一种模式在成年雄性和雌性大鼠的主动脉中重现,雌性大鼠的 TIMP-2 表达更高。成年雄性大鼠和雌性大鼠的肾下主动脉经 CaCl2(0.5 M)处理后,原位血管直径增加,尽管内侧弹性蛋白含量减少,但雌性大鼠的血管扩张明显较小。雌性大鼠经 CaCl2 处理的肾下主动脉更倾向于出现新内膜区域,这可能是原位扩张较小的部分原因,而新内膜的生长与原位直径的百分比变化呈正相关。新内膜的形成继发于内侧/近端血管平滑肌细胞(VSMC)密度的显著增加,这些细胞重新进入了 G2-M 期,而在经 CaCl2 处理的雄性大鼠肾下主动脉中,VSMC 细胞周期的重新进入被减弱了。因此,雌性 BAV 患者主动脉中更多的 TIMP-1 表达可能会阻止过度的弹性蛋白碎裂,雌性大鼠肾下主动脉经 CaCl2 处理后的新内膜优先生长代表了一种性别依赖性生物事件,它继发于结构蛋白的显著损失,限制了血管的扩张。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Greater TIMP‐1 protein levels and neointimal formation represent sex‐dependent cellular events limiting aortic vessel expansion in female rats
Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) and neointimal growth secondary to a reduction of medial elastin content represent sex‐dependent events limiting aortic vessel expansion in females. TIMP‐1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP‐2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2‐treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re‐entered the G2‐M phase whereas VSMC cell cycle re‐entry was attenuated in the CaCl2‐treated infrarenal aorta of male rats. Thus, greater TIMP‐1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2‐treatment of the infrarenal aorta of female rats represents a sex‐dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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