Apabetalone downregulates factors and pathways associated with vascular calcification

Gilham, Dean; Tsujikawa, Laura; Sarsons, Christopher D.; Halliday, Christopher; Wasiak, Sylwia; Stotz, Stephanie C.; Jahagirdar, Ravi; Sweeney, Michael; Johansson, Jan; Wong, Norman C.W.; Kalantar-Zadeh, Kamyar; Kulikowski, Ewelina

doi:10.1016/j.atherosclerosis.2018.11.002

Cited by 53 publications

(54 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RVX-208 reduces the expression of complement factors either in vitro or in mice and in CVD patients [189]. RVX-208 counters the trans-differentiation and calcification of VSMCs [190]. RVX-208 lowers serum alkaline phosphatase levels and improves CVD risk [191].…”

Section: Rvx-208 (Apabetalone)mentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

View full text Add to dashboard Cite

High-density lipoprotein (HDL) is a heterogeneous particle composed of apolipoproteins, enzymes, and lipids. Besides transporting cholesterol to the liver, HDL also exerts many protections on anti-oxidation, anti-inflammation, and anti-apoptosis. Initial understandings of HDL came from its protective roles against atherosclerosis and the observation that high plasma HDL cholesterol (HDL-C) levels seemed to decrease cardiovascular disease (CVD) attack. However, those patients either with cholesterol ester transfer protein (CETP) deficiency or taking CETP inhibitors substantially elevated HDL-C levels but did not necessarily decrease CVD risk. Thus, some researchers suggested that quantitative measurements of HDL particle (HDL-P) might be more valuable than traditional HDL-C measurements. What is more bewildering is that HDL from patients with systemic inflammation decreased its protective effects and even became a pro-inflammatory factor. Recently, synthesized HDL and apolipoprotein mimetic peptides showed biological functions similar to native ones. Expectedly, lots of novel measurement methods and therapeutic agents about HDL would be established soon.

show abstract

Section: Rvx-208 (Apabetalone)mentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

View full text Add to dashboard Cite

show abstract

“…Vascular calcification (VC) is prevalent in coronary artery disease, and its extent predicts cardiovascular risk [1]. Causes of calcification in atherosclerosis include dysregulated matrix metabolism, epitaxial mineral deposition, inflammation, oxidative stress, and apoptosis [2].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway

Chen

Zhou

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Mitochondrial fusion/mitophagy plays a role in cardiovascular calcification. Melatonin has been shown to protect against cardiovascular disease. This study sought to explore whether melatonin attenuates vascular calcification by regulating mitochondrial fusion/mitophagy via the AMP-activated protein kinase/optic atrophy 1 (AMPK/OPA1) signaling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red S staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure expression of runt-related transcription factor 2 (Runx2), mitofusin 2 (Mfn2), mito-light chain 3 (mito-LC3) II, and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were downregulated in response to melatonin, whereas Mfn2 and mito-LC3II were enhanced and accompanied by decreased mitochondrial superoxide levels. Melatonin also maintained mitochondrial function and promoted mitochondrial fusion/mitophagy via the OPA1 pathway. However, OPA1 deletion abolished the protective effects of melatonin on VSMC calcification. Melatonin treatment significantly increased p-AMPK and OPA1 protein expression, whereas treatment with compound C ablated the observed benefits of melatonin treatment. Collectively, our results demonstrate that melatonin protects VSMCs against calcification by promoting mitochondrial fusion/mitophagy via the AMPK/OPA1 pathway.

show abstract

“…After screening through 224 articles, we identified 66 original reports examining epigenetic processes in VC ( Figure 1). Interestingly, most reports (n = 40; 60.6%) looked into the pathogenic role of non-coding RNA in VC, while histone modification (n = 6; 9.1%) [53][54][55][56][57][58], DNA methylation (n = 8; 12.1%) [5,[59][60][61][62][63][64][65], and chromatin changes (n = 3; 4.5%) [66][67][68] accounted for one-fourth only. Nine (13.6%) [69][70][71][72][73][74][75][76][77] examined the discrepancy of epigenetic signatures between subjects or animals with and without VC but not their pathogenic influences.…”

Section: Strategy Of Literature Review and Findingsmentioning

confidence: 99%

“…SMARCA, a chromatin remodeler influencing chromatin structure and gene expression, has been shown to increase significantly in calcified rat aortas compared to non-calcified ones, and SMARCA upregulation might contribute to aberrant levels of VC-regulating miRNAs [68]. Gilham and colleagues demonstrated that molecules inhibiting chromatin modification site readers such as BET protein might help improve VC, but the findings were limited to in vitro only [67]. Although results from these three studies lend support to the notion that chromatin changes can be a unique signature of VC and even be pathogenic and druggable, more mechanistic research is expected to shed light on the specificity and the efficacy of such chromatin-oriented interventions for VC.…”

Section: Chromatin Changes In Vcmentioning

confidence: 99%

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

Hou

Yuan

et al. 2020

IJMS

View full text Add to dashboard Cite

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

show abstract

Apabetalone downregulates factors and pathways associated with vascular calcification

Cited by 53 publications

References 59 publications

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

Contact Info

Product

Resources

About