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Anti-inflammatory Effects of Statins in Lung Vascular Pathology: From Basic Science to Clinical Trials

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Lung Inflammation in Health and Disease, Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1303))

Abstract

HMG-CoA reductase inhibitors (or statins) are cholesterol-lowering drugs and are among the most widely prescribed medications in the United States. Statins exhibit pleiotropic effects that extend beyond cholesterol reduction including anti-atherosclerotic, antiproliferative, anti-inflammatory, and antithrombotic effects. Over the last 20 years, statins have been studied and examined in pulmonary vascular disorders, including both chronic pulmonary vascular disease such as pulmonary hypertension, and acute pulmonary vascular endothelial injury such as acute lung injury. In both research and clinical settings, statins have demonstrated promising vascular protection through modulation of the endothelium, attenuation of vascular leak, and promotion of endothelial repair following lung inflammation. This chapter provides a summary of the rapidly changing literature, summarizes the anti-inflammatory mechanism of statins on pulmonary vascular disorders, and explores clinical evidence for statins as a potential therapeutic approach to modulation of the endothelium as well as a means to broaden our understanding of pulmonary vasculopathy pathophysiology.

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Abbreviations

ITGB4:

Integrin β4

3’UTR:

3′ untranslated region

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

BAL:

Bronchoalveolar lavage

CAD:

Coronary artery disease

COPD:

Chronic obstructive pulmonary disorder

CpG:

CG dinucleotides

CRAC:

Ca2+-release-activated Ca2+

CVD:

Cardiovascular disease

DMNT:

DNA Methyltransferases

ECM:

Extracellular matrix

EMP:

Circulating endothelial microparticle

eNOS:

Endothelial nitric oxide synthase

EPC:

Endothelial progenitor cell

ET-1:

Endothelin-1

FA:

Focal adhesion

HARP trail:

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction trial

HAT:

Histone acetylase transferase

HDAC:

Histone deacetylases

ICU:

Intensive care unit

LBI:

Laminin-binding integrins

LCA:

Latent class analyses

MAPK:

Mitogen-activated protein kinase

miRNA:

microRNAs

MMP:

Matrix metalloproteases

MMP-9:

Matrix metallopeptidase 9

MPO:

Myeloperoxidase

PAK 4:

P21-activated kinase 4

PASMC:

Pulmonary arterial smooth muscle cell

PHD-3:

HIF1α-prolyl-4-hydroxylase 3

PVEC:

Pulmonary vascular endothelial cell

RISC:

RNA-induced silencing complex

ROS:

Reactive oxygen species

SAILS trail:

Statins for acutely injured lungs from Sepsis trial

SIRT1:

Silent information regulator 1

Treg:

Regulatory T-cell

VILI:

Ventilator-induced lung injury

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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ, USA

    Reem Faraj, Danyelle Paine & Ting Wang

  2. Department of Medicine, College of Medicine-Tucson, University of Arizona, Tucson, AZ, USA

    Stephen M. Black

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  1. Reem Faraj
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Correspondence to Stephen M. Black or Ting Wang .

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  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

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Faraj, R., Paine, D., Black, S.M., Wang, T. (2021). Anti-inflammatory Effects of Statins in Lung Vascular Pathology: From Basic Science to Clinical Trials. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume I. Advances in Experimental Medicine and Biology, vol 1303. Springer, Cham. https://doi.org/10.1007/978-3-030-63046-1_3

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