Statins with different lipophilic indices exert distinct effects on skeletal, cardiac and vascular smooth muscle

Irwin, J.; Fenning, Andrew; Vella, Rebecca

doi:10.1016/j.lfs.2019.117225

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…This could be advantageous, because liver is after all the main site of cholesterol biosynthesis, but due to their lipophilicity most statins can passively enter non-hepatic tissues, including brain, leading to side-effects. A recent study [44] assessed the effects of two shortacting statins with different hydrophobicities, showing that they produce different actions on skeletal, cardiac and vascular smooth muscle. Furthermore, hydrophilicity to a large extent determines the active transport mechanisms for entering the hepatocyte; due to their exclusion from non-hepatic tissues, statins with higher hydrophilicity turn out to be more hepato-selective.…”

Section: Structure and Permeabilitymentioning

confidence: 99%

Pleiotropic effects of statins on brain cells

Sodero

Barrantes

2020

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Section: Structure and Permeabilitymentioning

confidence: 99%

Pleiotropic effects of statins on brain cells

Sodero

Barrantes

2020

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Hydrophilic statins, due to the necessity to penetrate inside the cells by active transport, show a more hepatoselective effect, which means that other effects, apart from lipid-lowering activity, are less intense. Recent studies confirm this difference in the ability to produce pleiotropic effects after taking type 1 and type 2 statins [16].…”

Section: Statins-structure and Permeabilitymentioning

confidence: 91%

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

et al. 2021

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Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

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“…Low ROS levels are known to activate this pathway [78], whereas high to moderate ROS levels may be the result of long-term exposure to atorvastatin, leading to alterations in cardiac mitochondrial ultrastructure and mTOR inhibition [24]. The difference in inhibitory potency against mTOR between rosuvastatin and pravastatin may be related to their different ability to enter cells (due to different compound lipophilicity and HMGR inhibitory potency) [79], as we have also observed for the absence of an inhibitory effect of pravastatin on mitochon-drial activity in C2C12 myoblasts [19]. Moreover, lipophilic statins like lovastatin and simvastatin significantly increased mortality in cardiomyopathic hamsters and enhanced the stunning of myocardium in ischemic dogs [57,80].…”

Section: Undesired Effects Of Statins On Cardiomyocytesmentioning

confidence: 99%

Statins and Cardiomyocyte Metabolism, Friend or Foe?

Somers,

Siddiqi,

Morshuis

et al. 2023

JCDD

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Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, and are the cornerstone of lipid-lowering treatment. They significantly reduce cardiovascular morbidity and mortality. However, musculoskeletal symptoms are observed in 7 to 29 percent of all users. The mechanism underlying these complaints has become increasingly clear, but less is known about the effect on cardiac muscle function. Here we discuss both adverse and beneficial effects of statins on the heart. Statins exert pleiotropic protective effects in the diseased heart that are independent of their cholesterol-lowering activity, including reduction in hypertrophy, fibrosis and infarct size. Adverse effects of statins seem to be associated with altered cardiomyocyte metabolism. In this review we explore the differences in the mechanism of action and potential side effects of statins in cardiac and skeletal muscle and how they present clinically. These insights may contribute to a more personalized treatment strategy.

show abstract

Statins with different lipophilic indices exert distinct effects on skeletal, cardiac and vascular smooth muscle

Cited by 8 publications

References 51 publications

Pleiotropic effects of statins on brain cells

Pleiotropic effects of statins on brain cells

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

Statins and Cardiomyocyte Metabolism, Friend or Foe?

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