Experimental Data Snapshot

• Method: X-RAY DIFFRACTION
• Resolution: 2.40 Å
• R-Value Free: 0.284 
• R-Value Work: 0.238 
• R-Value Observed: 0.240 

• the LXR/RXR complex undergoes a conformational change that leads to the release of co-repressors and recruitment of co-activators, which modulates target gene expression. Altered LXR/RXR signaling contributes to development of HF risk factors and co-morbidities and, consequently, HF.

  HF = heart failure; LXR = liver X receptor; RXR = retinoid X receptor.

  Transcriptional activity of LXRs is induced in response to elevated cellular levels of cholesterol. Activation of LXRs normalizes reverse cholesterol transport, prevents diabetes-induced inflammation, and reduces the number of pro-inflammatory macrophages . Direct cardiac effects of LXR signaling include the decrease of cardiomyocyte hypertrophy, loss (death), and fibrotic remodeling. LXRs also stimulate angiogenesis within the myocardium and increase the capacity for glucose uptake and utilization (metabolic remodeling) (3).

  The aforementioned widespread effects of the LXRs provide an explanation for the contribution of altered LXRs signaling to the pathogenesis of several of HF co-morbidities, including atherosclerosis and vascular disease, hypertension, diabetes, obesity, and chronic kidney disease and consequently to HF 

• LXRシグナルが活性化すると心筋細胞は劣化することが確認されている　上図のアゴニストは人工物でX解析像を安定化させるために加えたものである
• シュミレイション上ではこのアゴニストは外して評価する
• LXRの肝臓での活性化は間接的には心筋に作用する
• Cirrhotic cardiomyopathy has been attributed to a cirrhotic proinflammatory state leading to increased cardiomyocyte apoptosis and shift in myosin heavy chain isoform from the a subtype to the weaker b isoform 
•  Circulatory abnormalities are predominantly due to liver-derived toxic factors causing arterial dilation and hyperdynamic circulation (50). With further progression of liver failure and arterial dilation, the cardiac systolic reserve is exhausted. From that point, the heart is unable to further increase the cardiac output, resulting in arterial underfilling and decreased effective circulatory volume 49, 50, 51.