Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Biomolecules. 2019 Nov 21;9(12):760. doi: 10.3390/biom9120760.
Aortic valve stenosis (AVS) is the most prevalent valvular heart disease in the Western World with exponentially increased incidence with age. If left untreated, the yearly mortality rates increase up to 25%. Currently, no effective pharmacological interventions have been established to treat or prevent AVS. The only treatment modality so far is surgical or transcatheter aortic valve replacement (AVR). Lipoprotein(a) [Lp(a)] has been implicated as a pivotal player in the pathophysiology of calcification of the valves. Patients with elevated levels of Lp(a) have a higher risk of hospitalization or mortality due to the presence of AVS. Multiple studies indicated Lp(a) as a likely causal and independent risk factor for AVS. This review discusses the most important findings and mechanisms related to Lp(a) and AVS in detail. During the progression of AVS, Lp(a) enters the aortic valve tissue at damaged sites of the valves. Subsequently, autotaxin converts lysophosphatidylcholine in lysophosphatidic acid (LysoPA) which in turn acts as a ligand for the LysoPA receptor. This triggers a nuclear factor-κB cascade leading to increased transcripts of interleukin 6, bone morphogenetic protein 2, and runt-related transcription factor 2. This progresses to the actual calcification of the valves through production of alkaline phosphatase and calcium depositions. Furthermore, this review briefly mentions potentially interesting therapies that may play a role in the treatment or prevention of AVS in the near future.
主动脉瓣狭窄（AVS）是西方世界最常见的瓣膜性心脏病，其发病率随年龄呈指数增长。如果不进行治疗，每年的死亡率高达 25%。目前，尚无有效的药物干预措施被证实可用于治疗或预防 AVS。迄今为止，唯一的治疗方法是手术或经导管主动脉瓣置换术（AVR）。脂蛋白(a)[Lp(a)]被认为是瓣膜钙化病理生理学中的关键因素。Lp(a)水平升高的患者因存在 AVS 而住院或死亡的风险更高。多项研究表明 Lp(a)是 AVS 的一个可能的因果和独立危险因素。本文详细讨论了与 Lp(a)和 AVS 相关的最重要的发现和机制。在 AVS 的进展过程中，Lp(a)进入瓣膜受损部位的主动脉瓣组织。随后，自分泌酶将溶血磷脂酰胆碱转化为溶血磷脂酸（LysoPA），LysoPA 反过来又作为 LysoPA 受体的配体。这触发核因子-κB 级联反应，导致白细胞介素 6、骨形态发生蛋白 2 和 runt 相关转录因子 2 的转录增加。这通过碱性磷酸酶的产生和钙沉积导致瓣膜的实际钙化。此外，本文还简要提及了一些可能在不久的将来对 AVS 的治疗或预防有作用的有前景的治疗方法。
