Department of Surgery, Laboratoire d'Études Moléculaires des Valvulopathies, Groupe de Recherche en Valvulopathies, Quebec Heart and Lung Institute/Research Center, Laval University, Quebec City, QC, Canada.
Eur J Clin Invest. 2013 Jun;43(6):570-8. doi: 10.1111/eci.12081. Epub 2013 Apr 1.
Calcific aortic valve disease (CAVD) is a chronic disorder characterized by a fibrocalcific remodelling. It is suspected that lipid retention within the aortic valve may be one important mechanism participating to aortic valve remodelling. Lipoprotein lipase (LPL) is implicated in lipid metabolism and may play a role in lipid retention within the aortic valve.
In 57 patients, CAVD were analysed for the expression of LPL by q-PCR and immunohistochemistry. Expression of oxidized-LDL (ox-LDL) and decorin was also documented. In addition, a complete blood profile, including the size of LDL and high-density lipoprotein (HDL) particles, were performed to find associations between the blood lipid profile and expression of ox-LDL and LPL within CAVD.
Immunohistochemistry studies revealed that LPL was expressed in stenotic aortic valves as a diffuse staining and also in dense cellular areas where macrophages were abundant. Expression of LPL co-localized with decorin and ox-LDL. In turn, valves with higher amount of ox-LDL had elevated number of LPL transcripts. In addition, we documented that the small, dense HDL phenotype was associated with an elevated amount of ox-LDL and LPL transcripts within CAVD. Furthermore, expression of LPL was associated with several indices of fibrocalcific remodelling of the aortic valve.
Expression of LPL within CAVD is related to the amount of ox-LDL, which is, in turn, associated with the small, dense HDL phenotype. Lipid retention associated with smaller HDL particles may participate in the expression of LPL, whereby a fibrocalcific remodelling of the aortic valve is promoted.
钙化性主动脉瓣疾病(CAVD)是一种以纤维钙化重塑为特征的慢性疾病。据推测,主动脉瓣内脂质蓄积可能是参与主动脉瓣重塑的一个重要机制。脂蛋白脂酶(LPL)参与脂质代谢,可能在主动脉瓣内脂质蓄积中发挥作用。
在 57 例患者中,通过 q-PCR 和免疫组织化学分析 CAVD 中 LPL 的表达。还记录了氧化型 LDL(ox-LDL)和核心蛋白聚糖的表达。此外,还进行了完整的血液分析,包括 LDL 和高密度脂蛋白(HDL)颗粒的大小,以寻找血液脂质谱与 CAVD 中 ox-LDL 和 LPL 表达之间的关联。
免疫组织化学研究表明,LPL 在狭窄的主动脉瓣中呈弥漫性染色,也在富含巨噬细胞的密集细胞区表达。LPL 的表达与核心蛋白聚糖和 ox-LDL 共定位。反过来,ox-LDL 含量较高的瓣膜中 LPL 转录本数量增加。此外,我们还记录到,小而致密的 HDL 表型与 CAVD 中 ox-LDL 和 LPL 转录本的含量升高有关。此外,LPL 的表达与主动脉瓣纤维钙化重塑的几个指数相关。
CAVD 中 LPL 的表达与 ox-LDL 的含量有关,而 ox-LDL 又与小而致密的 HDL 表型有关。与较小的 HDL 颗粒相关的脂质蓄积可能参与 LPL 的表达,从而促进主动脉瓣的纤维钙化重塑。