Endoplasmic reticulum stress activates unfolded protein response signaling and mediates inflammation, obesity, and cardiac dysfunction: Therapeutic and molecular approach

Omar Mohammed Amen, Satyajit D. Sarker, Reena Ghildyal, Aditya Arya

Research output: Contribution to journalArticle

Abstract

Obesity has been implicated as a risk factor for insulin resistance and cardiovascular diseases (CVDs). Although the association between obesity and CVD is a well-established phenomenon, the precise mechanisms remain incompletely understood. This has led to a relative paucity of therapeutic measures for the prevention and treatment of CVD and associated metabolic disorders. Recent studies have shed light on the pivotal role of prolonged endoplasmic reticulum stress (ERS)-initiated activation of the unfolded protein response (UPR), the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS). In this aspect, potential ways of attenuating ERS-initiated UPR signaling seem a promising avenue for therapeutic interventions. We review intersecting role of obesity-induced ERS, chronic inflammation, insulin resistance, and oxidative stress in the discovery of targeted therapy. Moreover, this review highlights the current progress and strategies on therapeutics being explored in preclinical and clinical research to modulate ERS and UPR signaling.

Original languageEnglish
Article number977
Pages (from-to)977
Number of pages21
JournalFrontiers in Pharmacology
Volume10
DOIs
Publication statusPublished - Sep 2019

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Unfolded Protein Response
Endoplasmic Reticulum Stress
Obesity
Inflammation
Cardiovascular Diseases
Insulin Resistance
Therapeutics
Cardiovascular System
Heat-Shock Proteins
Oxidative Stress
Insulin
Research

Cite this

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abstract = "Obesity has been implicated as a risk factor for insulin resistance and cardiovascular diseases (CVDs). Although the association between obesity and CVD is a well-established phenomenon, the precise mechanisms remain incompletely understood. This has led to a relative paucity of therapeutic measures for the prevention and treatment of CVD and associated metabolic disorders. Recent studies have shed light on the pivotal role of prolonged endoplasmic reticulum stress (ERS)-initiated activation of the unfolded protein response (UPR), the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS). In this aspect, potential ways of attenuating ERS-initiated UPR signaling seem a promising avenue for therapeutic interventions. We review intersecting role of obesity-induced ERS, chronic inflammation, insulin resistance, and oxidative stress in the discovery of targeted therapy. Moreover, this review highlights the current progress and strategies on therapeutics being explored in preclinical and clinical research to modulate ERS and UPR signaling.",
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Endoplasmic reticulum stress activates unfolded protein response signaling and mediates inflammation, obesity, and cardiac dysfunction: Therapeutic and molecular approach. / Amen, Omar Mohammed; Sarker, Satyajit D.; Ghildyal, Reena; Arya, Aditya.

In: Frontiers in Pharmacology, Vol. 10, 977, 09.2019, p. 977.

Research output: Contribution to journalArticle

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