An Unsettled Debate About the Potential Role of Infection in Pathogenesis of Atherosclerosis

Dahal, Udip; Sharma, Dikshya; Dahal, Kumud

doi:10.14740/jocmr3032w

Cited by 9 publications

(10 citation statements)

References 108 publications

(107 reference statements)

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“…On the cellular level, atherosclerosis is mainly characterized by endothelial dysfunction, but other cell types are also involved such as macrophages, T cells and smooth muscle cells. The activated endothelial cells show increased permeability and adhesion of immune cells, and change their normally anticoagulant state into a pro-coagulant state (Dahal et al, 2017;Ross, 1999).…”

Section: Atherosclerosismentioning

confidence: 99%

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Huwiler

Zangemeister‐Wittke

2018

Pharmacology & Therapeutics

172

134

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The immunomodulatory drug fingolimod (FTY720, Gilenya) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P subtype by induction of receptor downregulation. Since S1P is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression. Numerous preclinical studies have since been performed with the aim to increase the spectrum of potential indications for fingolimod with emphasis on other autoimmune disorders and diseases associated with inflammation and uncontrolled cell proliferation, including cancer. As an alternative to fingolimod, novel S1PR modulators with a more selective receptor activation profile and improved pharmacokinetic performance and tolerability have also been developed. Preclinical and clinical studies are ongoing to investigate their therapeutic potential. This review discusses the most relevant preclinical and clinical findings from S1PR-targeting and from less-well defined off-target effects reported in the literature, and reveals perspectives for using fingolimod and functionally-related derivatives and new formulations in the management of an increasing number of diseases.

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Section: Atherosclerosismentioning

confidence: 99%

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Huwiler

Zangemeister‐Wittke

2018

Pharmacology & Therapeutics

172

134

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“…One of the challenges consists in the multifactorial nature of proatherogenic properties of viral agents. The presence of more than one latent infection also complicates the identification of a correlation between the viruses and atherosclerosis [35]. In addition to direct viral effects on the endothelium, many viruses mediate indirect effects on the vascular wall through the activation of a systemic inflammatory response [36].…”

Section: Latent Viral Infections and Atherosclerosismentioning

confidence: 99%

“…These include the following viruses: Herpesviridae family viruses, enteroviruses, hepatitis viruses, influenza viruses, human immunodeficiency virus, and human papillomavirus. Bacterial infections also play a role, but this review focuses on the role of viruses in the development of atherosclerosis [33][34][35][36][37][38][39][40][41][42].…”

Section: Latent Viral Infections and Atherosclerosismentioning

confidence: 99%

Atherosclerosis. Macrophages. Viral infections

Рябов

Алексеева

Gombozhapova

et al. 2021

SMJ

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The emergence of new COVID-19 infection aggravated the existing issues and gave rise to new challenges associated with the impact of viruses on the atherosclerotic process and development of cardiovascular complications. Atherosclerosis is a multifactorial disease and its progression is largely determined by dyslipidemia and chronic low-grade systemic vascular inflammation. There are a number of viruses known to be involved in maintaining the inflammatory state through the prolonged viral persistence and replication in the macrophages whose plasticity changes due to the infection. The viruses can trigger the pro-atherogenic cytokine response through the diverse macrophage-dependent mechanisms. There is lack of data regarding impact of viral infections on the monocyte/macrophage plasticity and possible control of inflammation in atherogenesis. It is still unclear whether the relationships between the viral diseases and atherosclerosis are causal or merely associative. In this review, we summarize and critically analyze the current state of knowledge regarding the virus-related mechanisms promoting atherosclerosis.

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“…Hyperlipidemia and hypercholesterolemia are major biochemical risk factors for atherogenesis, which ultimately contribute to atherothrombosis with severe consequences. Currently, there is a small number of research articles dedicated to the structural changes in the aorta caused by hyperlipidemia and atherosclerosis as well as HSV-induced atherosclerosis [1]. Even less information is available on morphological studies of the aorta affected by a viral infection associated with atherogenesis.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural Features of Herpesvirus-Induced Aortic Intima Damage in Mice Fed the High-Fat Diet

et al. 2020

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The aim: To study the effect of a high-fat diet (HFD) on the structural changes in the aortic intima in intact and HSV-1-infected mice using Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). Materials and methods: In experiments Balb/c mice were infected with the HVS-1 and fed high-fat diet and 12 weeks later aortic ultrastructure was examined by SEM and TEM methods. The animals were subdivided into four experimental groups: 1st group – HSV-1-infected animals; 2nd – animals consuming high-fat diet (HFD); 3rd – infected animals that were subsequently consuming a high-fat diet (HSV / HFD); 4th – animals consuming a high-fat diet that were subsequently infected with HSV-1 (HFD / HSV) (n = 6); and control group – intact animals. Results: HVS-1 impaired ultrastructural changes in aorta greater than high-fat diet and HVS-1 alone (higher density of lipid inclusions in the subendothelial space, necrosis of endothelial cells), and infection of mice after high-fat diet ended 100% mortality. The formation of atheroma in the aortic wall during HFD was not detected, but the initiative manifestations of atherogenesis have been identified and restricted in the aortic intima. These structural changes included lipid inclusions in the subendothelial space, cell damage and destruction, which lead to an increase cellular detritus in the 3rd (HSV / HFD) group. Conclusions: HSV infection potentiates the accumulation of lipid inclusions in the aortic intima during a HFD, facilitates infection and contributes to the development of acute infection.

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An Unsettled Debate About the Potential Role of Infection in Pathogenesis of Atherosclerosis

Cited by 9 publications

References 108 publications

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Atherosclerosis. Macrophages. Viral infections

Ultrastructural Features of Herpesvirus-Induced Aortic Intima Damage in Mice Fed the High-Fat Diet

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