HIF in the heart: development, metabolism, ischemia, and atherosclerosis

Knutson, Andrew Kekūpa’a; Williams, Allison L; Boisvert, William A.; Shohet, Ralph V.

doi:10.1172/jci137557

Cited by 63 publications

(43 citation statements)

References 187 publications

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“…In vivo studies in LDL −/− mice have found that HIF-1 α deficiency in bone marrow cells substantially reduces atherosclerosis by a mechanism associated with HIF-1 α affecting its inflammatory properties [ 67 ]. In addition, HIF-1 α can also promote the formation and development of atherosclerosis by affecting glucose metabolism and apoptosis of macrophages, migration and proliferation of vascular smooth muscle cells, and permeability of endothelial cells [ 68 ].…”

Section: Pathophysiologic Mechanisms Underlying Osa-cih-induced Asmentioning

confidence: 99%

Intermittent Hypoxia and Atherosclerosis: From Molecular Mechanisms to the Therapeutic Treatment

Luo

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Intermittent hypoxia (IH) has a dual nature. On the one hand, chronic IH (CIH) is an important pathologic feature of obstructive sleep apnea (OSA) syndrome (OSAS), and many studies have confirmed that OSA-related CIH (OSA-CIH) has atherogenic effects involving complex and interacting mechanisms. Limited preventive and treatment methods are currently available for this condition. On the other hand, non-OSA-related IH has beneficial or detrimental effects on the body, depending on the degree, duration, and cyclic cycle of hypoxia. It includes two main states: intermittent hypoxia in a simulated plateau environment and intermittent hypoxia in a normobaric environment. In this paper, we compare the two types of IH and summarizes the pathologic mechanisms and research advances in the treatment of OSA-CIH-induced atherosclerosis (AS), to provide evidence for the systematic prevention and treatment of OSAS-related AS.

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Section: Pathophysiologic Mechanisms Underlying Osa-cih-induced Asmentioning

confidence: 99%

Intermittent Hypoxia and Atherosclerosis: From Molecular Mechanisms to the Therapeutic Treatment

Luo

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The relationship between HIF-1α and atherosclerosis is well documented and has been reviewed previously ( 14 , 15 ). While several levels of evidence support the hypothesis that HIF-1α could be pro-atherogenic within atheroma plaques ( 10 ), experimental models of atherosclerosis in mice suggest a complex role that depends on the cell type or the organ in which HIF-1α is present ( 16 , 17 ).…”

Section: Hif-1α and Atherosclerosismentioning

confidence: 98%

Cholesterol and HIF-1α: Dangerous Liaisons in Atherosclerosis

2022

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HIF-1α exerts both detrimental and beneficial actions in atherosclerosis. While there is evidence that HIF-1α could be pro-atherogenic within the atheromatous plaque, experimental models of atherosclerosis suggest a more complex role that depends on the cell type expressing HIF-1α. In atheroma plaques, HIF-1α is stabilized by local hypoxic conditions and by the lipid microenvironment. Macrophage exposure to oxidized LDLs (oxLDLs) or to necrotic plaque debris enriched with oxysterols induces HIF-1α -dependent pathways. Moreover, HIF-1α is involved in many oxLDL-induced effects in macrophages including inflammatory response, angiogenesis and metabolic reprogramming. OxLDLs activate toll-like receptor signaling pathways to promote HIF-1α stabilization. OxLDLs and oxysterols also induce NADPH oxidases and reactive oxygen species production, which subsequently leads to HIF-1α stabilization. Finally, recent investigations revealed that the activation of liver X receptor, an oxysterol nuclear receptor, results in an increase in HIF-1α transcriptional activity. Reciprocally, HIF-1α signaling promotes triglycerides and cholesterol accumulation in macrophages. Hypoxia and HIF-1α increase the uptake of oxLDLs, promote cholesterol and triglyceride synthesis and decrease cholesterol efflux. In conclusion, the impact of HIF-1α on cholesterol homeostasis within macrophages and the feedback activation of the inflammatory response by oxysterols via HIF-1α could play a deleterious role in atherosclerosis. In this context, studies aimed at understanding the specific mechanisms leading to HIF-1α activation within the plaque represents a promising field for research investigations and a path toward development of novel therapies.

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“…HIF is a nuclear transcription factor that facilitates cells to adapt to the hypoxic environment ( Knutson et al, 2021 ; Cowman and Koh 2022 ). Liu et al, found that upregulation of gastric carcinoma proliferation enhancing transcript 1 (GHET1) positively correlated with tumor size, metastasis, proliferation, and colony formation in OC patients ( Liu and Li 2019 ).…”

Section: The Regulatory Mechanism Of Ncrnas In the Glycolysis Of Ovar...mentioning

confidence: 99%

Noncoding RNAs in the Glycolysis of Ovarian Cancer

Zhang

Liu

2022

Front. Pharmacol.

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Energy metabolism reprogramming is the characteristic feature of tumors. The tumorigenesis, metastasis, and drug resistance of ovarian cancer (OC) is dependent on energy metabolism. Even under adequate oxygen conditions, OC cells tend to convert glucose to lactate, and glycolysis can rapidly produce ATP to meet their metabolic energy needs. Non-coding RNAs (ncRNAs) interact directly with DNA, RNA, and proteins to function as an essential regulatory in gene expression and tumor pathology. Studies have shown that ncRNAs regulate the process of glycolysis by interacting with the predominant glycolysis enzyme and cellular signaling pathway, participating in tumorigenesis and progression. This review summarizes the mechanism of ncRNAs regulation in glycolysis in OC and investigates potential therapeutic targets.

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HIF in the heart: development, metabolism, ischemia, and atherosclerosis

Cited by 63 publications

References 187 publications

Intermittent Hypoxia and Atherosclerosis: From Molecular Mechanisms to the Therapeutic Treatment

Intermittent Hypoxia and Atherosclerosis: From Molecular Mechanisms to the Therapeutic Treatment

Cholesterol and HIF-1α: Dangerous Liaisons in Atherosclerosis

Noncoding RNAs in the Glycolysis of Ovarian Cancer

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