Effect of anti-hyperglycemic drugs on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells

Kapadia, Poonam; Bikkina, Priyanka; Landicho, Marie Angelica; Parekh, Shrina; Haas, Michael J.; Mooradian, Arshag D.

doi:10.1016/j.ejphar.2021.174249

Cited by 26 publications

(15 citation statements)

References 31 publications

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“…Although investigations in animals are scarce, studies among humans have suggested that GLP-1 RAs directly mitigate the development of coronary atherosclerosis through several mechanisms ( Garg et al, 2019 ) ( Table 1 ). First, GLP-1 RAs can improve endothelial function and reduce oxidative stress in coronary arteries ( Erdogdu et al, 2010 , 2013 ; Kapadia et al, 2021 ). Accordingly, GLP-1 receptors were detected in human coronary artery endothelial cells (hCAECs) ( Nyström et al, 2004 ).…”

Section: Glucagon-like Peptide 1 Receptor Agonists and Pathways Under...mentioning

confidence: 99%

“…These mechanisms were mediated by the GLP-1 receptor and involved protein kinase A (PKA), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and endothelial nitric oxide synthase (eNOS) pathways. In another study performed in hCAECs, exendin-4, liraglutide, albiglutide, and lixisenatide led to a decrease in endoplasmic reticulum stress by downregulating the unfolded protein response ( Kapadia et al, 2021 ).…”

Section: Glucagon-like Peptide 1 Receptor Agonists and Pathways Under...mentioning

confidence: 99%

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GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events

et al. 2022

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Objective: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) lower plasma glucose through effects on insulin and glucagon secretion and by decelerating gastric emptying. GLP-1 RAs have many beneficial effects beyond glycemic control, including a protective role on the cardiovascular system. However, underlying mechanisms linking GLP-1 RAs with coronary artery disease are complex and not fully elucidated. In this mini-review, we discuss these mechanisms and subsequent clinical events.Data Sources: We searched PubMed and Google Scholar for evidence on GLP-1 RAs and coronary events. We did not apply restrictions on article type. We reviewed publications for clinical relevance.Synopsis of Content: In the first part, we review the current evidence concerning the role of GLP-1 RAs on potential mechanisms underlying the development of coronary events. Specifically, we discuss the role of GLP-1 RAs on atherosclerosis and vasospasms of epicardial coronary arteries, as well as structural/functional changes of coronary microvasculature. In the second part, we summarize the clinical evidence on the impact of GLP-1 RAs in the prevention of acute and chronic coronary syndromes and coronary revascularization. We conclude by discussing existing gaps in the literature and proposing directions for future research.

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Section: Glucagon-like Peptide 1 Receptor Agonists and Pathways Under...mentioning

confidence: 99%

Section: Glucagon-like Peptide 1 Receptor Agonists and Pathways Under...mentioning

confidence: 99%

GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events

et al. 2022

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“…Diabetic cardiomyopathy is characterized by diastolic dysfunction and left ventricular hypertrophy ultimately followed by heart failure with preserved ejection fraction [ 48 ]. There remains no targeted treatment, although there is optimism around the newer glucose lowering drugs which may buffer ER stress pathways linked to the unfolded protein response and autophagy [ 49 ]. These drugs may be beneficial for heart failure even in people without T2DM [ 49 ].…”

Section: Oxylipins and Complications Of Diabetesmentioning

confidence: 99%

“…There remains no targeted treatment, although there is optimism around the newer glucose lowering drugs which may buffer ER stress pathways linked to the unfolded protein response and autophagy [ 49 ]. These drugs may be beneficial for heart failure even in people without T2DM [ 49 ].…”

Section: Oxylipins and Complications Of Diabetesmentioning

confidence: 99%

“…Cardiomyocyte autophagy is decreased in mouse models of T2DM [ 48 ]. In human coronary endothelial cells treated with dextrose, co-treatment with either liraglutide, dapagliflozin, or metformin, returned markers of ER stress/unfolded protein response to baseline levels seen in control cells [ 49 ]; however, the effects of these drugs on tunicamycin-induced ER stress markers was incomplete, suggesting a place for alternative strategies in the future pharmacological armamentarium. The CYP-sEH pathway may be one such target.…”

Section: Oxylipins and Complications Of Diabetesmentioning

confidence: 99%

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Soluble Epoxide Hydrolase and Diabetes Complications

Anita

Swardfager

2022

IJMS

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Type 2 diabetes mellitus (T2DM) can result in microvascular complications such as neuropathy, retinopathy, nephropathy, and cerebral small vessel disease, and contribute to macrovascular complications, such as heart failure, peripheral arterial disease, and large vessel stroke. T2DM also increases the risks of depression and dementia for reasons that remain largely unclear. Perturbations in the cytochrome P450-soluble epoxide hydrolase (CYP-sEH) pathway have been implicated in each of these diabetes complications. Here we review evidence from the clinical and animal literature suggesting the involvement of the CYP-sEH pathway in T2DM complications across organ systems, and highlight possible mechanisms (e.g., inflammation, fibrosis, mitochondrial function, endoplasmic reticulum stress, the unfolded protein response and autophagy) that may be relevant to the therapeutic potential of the pathway. These mechanisms may be broadly relevant to understanding, preventing and treating microvascular complications affecting the brain and other organ systems in T2DM.

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Sodium‐Glucose Cotransporter‐2 Inhibitor Suppresses Endoplasmic Reticulum Stress and Oxidative Stress in Diabetic Nephropathy Through Nrf2 Signaling: A Clinical and Experimental Study

Prasad,

Victor,

Ganesh

et al. 2024

The Journal of Clinical Pharma

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Diabetic nephropathy (DN), a severe complication of type 2 diabetes mellitus (T2DM), is marked by heightened endoplasmic reticulum stress (ERS) and oxidative stress (OS) due to protein misfolding and free radical generation. We investigated the sodium‐glucose co‐transporter‐2 inhibitor (SGLT2i), canagliflozin (Cana), in alleviating ERS and OS in DN patients and THP‐1 cells under hyperglycemic condition. A total of 120 subjects were divided into four groups, with 30 subjects in each group: healthy controls, T2DM individuals, DN patients receiving standard treatment, and those treated with Cana. The control group had no history of diabetes, cardiovascular or renal diseases, or other comorbidities. Cana was administered at doses of either 100 or 300 mg per day based on the estimated glomerular filtration rate (eGFR) value of DN individuals, with a mean follow‐up of 6 months. Additionally, THP‐1 monocytes were exposed to HGM (33.3 mM glucose with a cytokine cocktail of TNF‐α and IFN‐γ at 50 ng/mL each) to evaluate the relative levels of ERS, OS markers, and nuclear factor erythroid 2‐related factor 2 (Nrf2), the transcription factor regulating cellular redox, which is downregulated in diabetes. Our results revealed that ERS markers GRP78 and PERK, as well as OS markers TXNIP and p22phox, were elevated in both DN patients and HGM‐treated THP‐1 monocytes and were reduced by Cana intervention. Furthermore, Cana regulated the phosphorylation of Nrf2, Akt, and EIF2α in HGM‐treated monocytes. In conclusion, our findings highlight the role of Cana in activating Nrf2, thereby attenuating ERS and OS to mitigate DN progression.

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Effect of anti-hyperglycemic drugs on endoplasmic reticulum (ER) stress in human coronary artery endothelial cells

Cited by 26 publications

References 31 publications

GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events

GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events

Soluble Epoxide Hydrolase and Diabetes Complications

Sodium‐Glucose Cotransporter‐2 Inhibitor Suppresses Endoplasmic Reticulum Stress and Oxidative Stress in Diabetic Nephropathy Through Nrf2 Signaling: A Clinical and Experimental Study

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