The Role of High-Density Lipoproteins in Endothelial Cell Metabolism and Diabetes-Impaired Angiogenesis

Primer, K.; Psaltis, Peter J.; Tan, Joanne; Bursill, Christina A.

doi:10.3390/ijms21103633

Cited by 19 publications

(19 citation statements)

References 74 publications

(122 reference statements)

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“…In general, type 2 diabetes is associated with increased fatty acid utilization and reduced glucolytic metabolism. Notably, pathways that allow endothelial cells to upregulate glycolysis in response to hypoxia are impaired in diabetes (15). Dodd et al (16) reported that reduced succinate content leads to decreased hypoxia-inducible factor 1-a (HIF1-a) signaling in diabetic hearts.…”

Section: Introductionmentioning

confidence: 99%

The Impaired Bioenergetics of Diabetic Cardiac Microvascular Endothelial Cells

et al. 2021

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Diabetes causes hyperglycemia, which can create a stressful environment for cardiac microvascular endothelial cells (CMECs). To investigate the impact of diabetes on the cellular metabolism of CMECs, we assessed glycolysis by quantifying the extracellular acidification rate (ECAR), and mitochondrial oxidative phosphorylation (OXPHOS) by measuring cellular oxygen consumption rate (OCR), in isolated CMECs from wild-type (WT) hearts and diabetic hearts (db/db) using an extracellular flux analyzer. Diabetic CMECs exhibited a higher level of intracellular reactive oxygen species (ROS), and significantly reduced glycolytic reserve and non-glycolytic acidification, as compared to WT CMECs. In addition, OCR assay showed that diabetic CMECs had increased maximal respiration, and significantly reduced non-mitochondrial oxygen consumption and proton leak. Quantitative PCR (qPCR) showed no difference in copy number of mitochondrial DNA (mtDNA) between diabetic and WT CMECs. In addition, gene expression profiling analysis showed an overall decrease in the expression of essential genes related to β-oxidation (Sirt1, Acox1, Acox3, Hadha, and Hadhb), tricarboxylic acid cycle (TCA) (Idh-3a and Ogdh), and electron transport chain (ETC) (Sdhd and Uqcrq) in diabetic CMECs compared to WT CMECs. Western blot confirmed that the protein expression of Hadha, Acox1, and Uqcrq was decreased in diabetic CMECs. Although lectin staining demonstrated no significant difference in capillary density between the hearts of WT mice and db/db mice, diabetic CMECs showed a lower percentage of cell proliferation by Ki67 staining, and a higher percentage of cellular apoptosis by TUNEL staining, compared with WT CMECs. In conclusion, excessive ROS caused by hyperglycemia is associated with impaired glycolysis and mitochondrial function in diabetic CMECs, which in turn may reduce proliferation and promote CMEC apoptosis.

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Section: Introductionmentioning

confidence: 99%

The Impaired Bioenergetics of Diabetic Cardiac Microvascular Endothelial Cells

et al. 2021

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“…Nowadays, it is widely accepted that HDL are a class of natural nanoparticles that display pleiotropic functions, such as RCT, anti-inflammatory action, immunity, antioxidative effects, and antithrombotic action [ 7 , 8 , 9 , 10 ]. Proteomics, lipidomics, and the analysis of small RNA in HDL particles are uncovering more and more of the functions of HDL.…”

Section: Introductionmentioning

confidence: 99%

High-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma

Kudinov

Alekseeva

Torkhovskaya

et al. 2020

IJMS

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It is well known that blood lipoproteins (LPs) are multimolecular complexes of lipids and proteins that play a crucial role in lipid transport. High-density lipoproteins (HDL) are a class of blood plasma LPs that mediate reverse cholesterol transport (RCT)—cholesterol transport from the peripheral tissues to the liver. Due to this ability to promote cholesterol uptake from cell membranes, HDL possess antiatherogenic properties. This function was first observed at the end of the 1970s to the beginning of the 1980s, resulting in high interest in this class of LPs. It was shown that HDL are the prevalent class of LPs in several types of living organisms (from fishes to monkeys) with high resistance to atherosclerosis and cardiovascular disorders. Lately, understanding of the mechanisms of the antiatherogenic properties of HDL has significantly expanded. Besides the contribution to RCT, HDL have been shown to modulate inflammatory processes, blood clotting, and vasomotor responses. These particles also possess antioxidant properties and contribute to immune reactions and intercellular signaling. Herein, we review data on the structure and mechanisms of the pleiotropic biological functions of HDL from the point of view of their evolutionary role and complex dynamic nature.

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“…In addition, Poznyak et al discuss the current knowledge concerning the mechanisms by which diabetes mellitus promotes the atherogenic process, and summarize the physiopathological hallmarks linking atherosclerosis and diabetes mellitus, such as protein kinase signaling, oxidative stress, miRNA alterations and epigenetic changes [11]. The breakdown of homeostatic regulation of lipids occurring during diabetes has also been examined by Primer and collaborators [12]. In particular, they summarize the current understanding of endothelial cell metabolism and its dysregulation during diabetes and discuss the different mechanisms by which high-density lipoproteins (HDL) modulate endothelial cell metabolic reprogramming and counteract diabetes-impaired angiogenesis.…”

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confidence: 99%