The effect of statins on the organs: similar or contradictory?

Ahmadi, Yasin; Ghorbanihaghjo, Amir; Argani, Hassan

doi:10.15171/jcvtr.2017.11

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…In addition to inhibition of HMG-CoAR, statins have demonstrated actions at the transcription level, with increases in nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα), mediated by the Rho-signaling pathway, potentially explaining increases in high-density lipoprotein cholesterol (HDL-C) levels with statin therapy [ 32 ]. Statins also influence the expression of a wide range of other genes, including transcription factors involved in inflammation, proliferation, and differentiation [ 33 , 34 ], and cholesterol transporters in a range of tissues, including the liver, intestine, adipose tissue, and skin, and apolipoprotein A1 (apo-A1) in the liver ( Figure 2 ) [ 35 ]. This leads to an increased transfer of cholesterol to apo-A1, leading to a greater production of HDL.…”

Section: Effect Of Ryr On Ldl-c Plasma Level and Estimated Risk Of Ascvdmentioning

confidence: 99%

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

et al. 2023

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Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15–34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy.

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Section: Effect Of Ryr On Ldl-c Plasma Level and Estimated Risk Of Ascvdmentioning

confidence: 99%

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

et al. 2023

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“…The fact that purified human anti-HMGCR antibodies are directed against some rat liver cells is not surprising because hepatocytes are responsible for the synthesis of 60-70% of the cholesterol for the whole body [9]. HMGCR is mainly expressed in periportal hepatocytes, as reflected by the HALIP.…”

Section: Discussionmentioning

confidence: 99%

Anti-HMGCR Specificity of HALIP: A Confirmatory Study

Baucells

Martínez

Alvarado-Cárdenas

et al. 2020

Journal of Immunology Research

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A distinctive new indirect immunofluorescence pattern in liver tissue has been associated with anti-HMGCR autoantibodies. It is known as HALIP (HMGCR Associated Liver Immunofluorescence Pattern). In this study, we furthered the original studies to demonstrate the association of anti-HMGCR antibodies with the HALIP. Human anti-HMGCR antibodies from patients’ sera were purified and incubated with rat triple tissue (kidney/stomach/liver). A characteristic HALIP was observed. Additionally, a colocalization assay of human anti-HMGCR antibodies with rabbit polyclonal anti-HMGCR antibodies showed colocalization of both immunofluorescence patterns. This study confirms that the HALIP is due to human anti-HMGCR antibodies.

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“…It has previously been suggested that statins may prevent the formation and rupture of aneurysms[4], but this finding has been refuted by other studies which find no effect[5,6]. Interestingly, statins can have the effect of either increasing or decreasing macrophage-mediated cholesterol efflux, though with an overall preference for inhibiting this process[39]. This would lend theoretical mechanistic credibility to the potential utility of statins as a rupture-prevention therapy via the reduction of macrophage-associated cholesterol efflux (found to be associated with rupture in our results).…”

Section: Discussionmentioning

confidence: 99%

Microenvironment of ruptured cerebral aneurysms discovered using data driven analysis of gene expression

et al. 2019

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Background It is well known that ruptured intracranial aneurysms are associated with substantial morbidity and mortality, yet our understanding of the genetic mechanisms of rupture remains poor. We hypothesize that applying novel techniques to the genetic analysis of aneurysmal tissue will yield key rupture-associated mechanisms and novel drug candidates for the prevention of rupture. Methods We applied weighted gene co-expression networks (WGCNA) and population-specific gene expression analysis (PSEA) to transcriptomic data from 33 ruptured and unruptured aneurysm domes. Mechanisms were annotated using Gene Ontology, and gene network/population-specific expression levels correlated with rupture state. We then used computational drug repurposing to identify plausible drug candidates for the prevention of aneurysm rupture. Results Network analysis of bulk tissue identified multiple immune mechanisms to be associated with aneurysm rupture. Targeting these processes with computational drug repurposing revealed multiple candidates for preventing rupture including Btk inhibitors and modulators of hypoxia inducible factor. In the macrophage-specific analysis, we identify rupture-associated mechanisms MHCII antigen processing, cholesterol efflux, and keratan sulfate catabolism. These processes map well onto several of highly ranked drug candidates, providing further validation. Conclusions Our results are the first to demonstrate population-specific expression levels and intracranial aneurysm rupture, and propose novel drug candidates based on network-based transcriptomics.

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The effect of statins on the organs: similar or contradictory?

Cited by 10 publications

References 46 publications

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Anti-HMGCR Specificity of HALIP: A Confirmatory Study

Microenvironment of ruptured cerebral aneurysms discovered using data driven analysis of gene expression

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