High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase

Yuhanna, Ivan S.; Zhu, Yan; Cox, Blair E.; Hahner, Lisa; Osborne-Lawrence, Sherri; Lu, Ping; Marcel, Yves L.; Anderson, Richard G. W.; Mendelsohn, Michael E.; Hobbs, Helen H.; Shaul, Philip W.

doi:10.1038/89986

Cited by 668 publications

(513 citation statements)

References 31 publications

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“…Systemically, high HDL concentrations have been associated with decreased inflammatory cytokine levels and decreased systemic oxidative stress via associated antioxidant enzymes and by acting as acceptors of prooxidant lipids 13, 17, 18, 19, 20. In addition, high HDL concentrations are associated with decreased endothelial adhesion molecule expression, increased endothelial nitric oxide production, and decreased endothelial damage 14, 16, 17. Decreased HDL anti‐inflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease 32, 33, 34, 35.…”

Section: Discussionmentioning

confidence: 99%

“…High‐density lipoproteins (HDLs) have systemic anti‐inflammatory and antioxidant properties and limit endothelial dysfunction and damage by attenuating endothelial cell activation and adhesion molecule expression, by activating endothelial nitric oxide synthase, and by promoting endothelial repair 10, 13, 14, 15, 16, 17, 18, 19, 20. In critically ill patients with pneumonia or sepsis, low HDL cholesterol concentrations are associated with multiorgan dysfunction and short‐ and long‐term death 21, 22.…”

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confidence: 99%

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High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.Methods and ResultsWe tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003).ConclusionsA higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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“…Interestingly, HDL binding to SR-BI increases eNOS activity. 55 To further support the proangiogenic role of HDL, previous studies have shown that HDL can promote endothelial cell proliferation. 56 In agreement with this interpretation, inhibition of eNOS via N(G)-nitro-L-arginine methyl ester administration inhibits tumor angiogenesis.…”

Section: Role Of Lipoproteins In Tumor Formationmentioning

confidence: 99%

Role of Cholesterol in the Development and Progression of Breast Cancer

Llaverı́as

Danilo

Mercier

et al. 2011

The American Journal of Pathology

262

229

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Breast cancer is the most commonly occurring cancer in women in Western societies. 1 It is estimated that 207,090 new cases will be diagnosed and that in the United States, 39,840 women will die of the disease in 2010 (American Cancer Society, Cancer Facts & Figures 2010, http://www. cancer.org/Research/cancer-facts-and-figures-2010, last accessed November 15, 2010. Interestingly, the incidence is about 5 times higher in Western countries than in developing countries. 2 Moreover, relocation and migrational studies have demonstrated that migration from a region with low incidence to a region with high incidence increases breast cancer incidence in the immigrant population. 3 These observations suggest a strong environmental influence on breast cancer development.Diet and obesity are now considered important risk factors for cancer development. 4,5 However, despite major modifications of its metabolism during obesity development and its function in tissue pathogenesis, little is known about the metabolism and role of plasma cholesterol in cancer development. Epidemiological studies have demonstrated that patients with cancer have abnormal levels of high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol, 6,7 which are the major lipoprotein carriers of cholesterol in human plasma. In addition, numerous studies have established that transformed cells and tumors exhibit abnormal regulation of several genes that are under the control of cholesterol. The products of these genes include the LDL receptor (LDL-R), hydroxy-methyl-glutaryl coenzyme A reductase (HMG-CoA Reductase), and their regulators, the sterol regulatory element binding proteins. 8 -13 As a consequence, these genes are dysregulated at the transcriptional level during tumorigenesis. These data suggest that transformed cells may require or utilize more cholesterol than normal cells, and this may be associated with their increased rate of proliferation. More recent studies have implicated HDL during tumor formation in breast cancer. 14 -16 However, their precise function remains controversial. The present study was performed to test the hypothesis that dietary cholesterol and plasma cholesterol levels have an important role in the regulation of breast cancer onset and progression.

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“…For instance, diabetic persons often have poor peripheral circulation, which leads to ischemic injury, impaired wound healing, and impaired vision, all of which involve altered endothelial cell function that relates to endothelial nitric oxide (NO) synthase (eNOS) and the generation of NO (2,21). Several studies have shown that HDL acting through its receptor, SR-BI, can stimulate eNOS to produce NO (4,16,24,36). Interestingly, both calcium-dependent and calcium-independent mechanisms have been shown to account for HDL-mediated NO generation.…”

mentioning

confidence: 99%

Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

White

Guerin

Swanson

et al. 2008

American Journal of Physiology-Cell Physiology

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Smart EJ. Diabetic HDL-associated myristic acid inhibits acetylcholineinduced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin. Am J Physiol Cell Physiol 294: C295-C305, 2008. First published October 31, 2007 doi:10.1152/ajpcell.00042.2007.-In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients. fatty acid; lipoprotein; diabetes; signaling CARDIOVASCULAR DISEASES are influenced by both genetic and environmental factors that can negatively or positively influence the development and progression of cardiovascular diseases, such as plasma levels of LDL and HDL (25,26). High plasma levels of LDL promote the accumulation of cholesterol in vessel wall macrophages and the formation of atherosclerotic plaque (3,

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High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase

Cited by 668 publications

References 31 publications

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Role of Cholesterol in the Development and Progression of Breast Cancer

Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

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