High-density lipoprotein therapeutics and cardiovascular prevention

Fazio, Sergio; Linton, MacRae F.

doi:10.1016/j.jacl.2010.08.004

Cited by 25 publications

(23 citation statements)

References 94 publications

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“…One the other hand, earlier studies have indicated that fibrates are related to anemia in patients with DN [100]. Their mode of action involves certain nuclear receptors (perixosome proliferator-activated receptors); however, their exact mechanism of action has not been completely elucidated [30,101]. Fibrates reduce the oxygen affinity of Hb and cause oxygen release in the tissues, thus removing the stimulating role of tissue hypoxia for EPO synthesis [102][103][104].…”

Section: Medicationsmentioning

confidence: 99%

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Παππά¹,

Dounousi

Duni

et al. 2015

Int Urol Nephrol

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Diabetes mellitus (DM) is currently considered a modern global epidemic, and diabetic nephropathy (DN) is the most common cause of chronic kidney disease (CKD). Anemia is one of the most significant complications of CKD, and it is mainly attributed to insufficient erythropoietin (EPO) production. However, anemia develops earlier in the course of CKD among patients with DM, and the severity of anemia tends to be more marked in these patients compared to nondiabetic subjects, regardless of the stage of CKD. In this review, we focus on the "less known" complex interacting mechanisms which are involved in the pathophysiology of anemia associated with DN. Although the major cause of anemia in DN is considered to be an inappropriate response of the plasma EPO concentration to anemia, several other possible mechanisms have been suggested. Glomerular hyperfiltration, proteinuria, renal tubular dysfunction and interstitial fibrosis are among the main culprits. On the other hand, systemic effects such as chronic inflammation, autonomic neuropathy and the renin-angiotensin system are also involved. Finally, several medications are considered to aggravate anemia associated with DN. Since anemia is an important predictor of quality of life and is implicated in the increased burden of cardiovascular morbidity and mortality, further research is required to elucidate its pathogenesis in diabetic patients.

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Section: Medicationsmentioning

confidence: 99%

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Παππά¹,

Dounousi

Duni

et al. 2015

Int Urol Nephrol

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“…Primary antibodies for ABCA1 and LDL CHD compared with control subjects (8)(9)(10)(11)(12). These functional properties of HDL are known to predict CHD risk independently of HDL cholesterol levels ( 4,(13)(14)(15)(16)(17). However, due to the chronic nature of cardiovascular disease in humans, it is unclear how acute changes in metabolism result in changes in HDL composition.…”

Section: Western Blotsmentioning

confidence: 99%

Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones

Martinez¹,

Emfinger

Overton

et al. 2012

Journal of Lipid Research

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Impairment in HDL function associated with obesity and elevated serum triglyceride (TG) may be a major contributor to risk of coronary heart disease (CHD) in obese patients, yet mechanisms by which changes in metabolism impair HDL function are not well defi ned ( 1-6 ). Increased TGs in the form of VLDL give rise to low levels of HDL in part due to the actions of cholesteryl ester transfer protein (CETP), which shuttles TG and cholesteryl esters between serum lipoproteins. Because of lipid exchange, elevated serum VLDL leads to TG enrichment of HDL. This TG enrichment reduces the affinity of apolipoprotein A1 (apoA1) for cholesterol, promotes clearance of apoA1, and decreases HDL particle number ( 1, 3, 7 ). In addition, changes in the function of HDL related to infl ammation, coagulation, and reverse cholesterol transport are associated with obesity and metabolic diseases. HDL proteomics have revealed changes in apolipoproteins, infl ammatory proteins, and coagulation proteins in individuals with known Abstract Mechanisms underlying changes in HDL composition caused by obesity are poorly defi ned, partly because mice lack expression of cholesteryl ester transfer protein (CETP), which shuttles triglyceride and cholesteryl ester between lipoproteins. Because menopause is associated with weight gain, altered glucose metabolism, and changes in HDL, we tested the effect of feeding a high-fat diet (HFD) and ovariectomy (OVX) on glucose metabolism and HDL composition in CETP transgenic mice. After OVX, female CETP-expressing mice had accelerated weight gain with HFDfeeding and impaired glucose tolerance by hyperglycemic clamp techniques, compared with OVX mice fed a low-fat diet (LFD). Sham-operated mice (SHAM) did not show HFDinduced weight gain and had less glucose intolerance than OVX mice. Using shotgun HDL proteomics, HFD-feeding in OVX mice had a large effect on HDL composition, including increased levels of apoA2, apoA4, apoC2, and apoC3, proteins involved in TG metabolism. These changes were associated with decreased hepatic expression of SR-B1, ABCA1, and LDL receptor, proteins involved in modulating the lipid content of HDL. In SHAM mice, there were minimal changes in HDL composition with HFD feeding. These studies suggest that the absence of ovarian hormones negatively infl uences the response to high-fat feeding in terms of glucose tolerance and HDL composition. CETP-expressing mice may represent a useful model to defi ne how metabolic changes affect HDL composition and function.

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“…The trial was terminated prematurely after a median of 550 days because of an excess of deaths, myocardial infarctions, angina, revascularizations procedures, and heart failure among patients receiving torcetrapib plus atorvastatin as compared to atorvastatin alone. These adverse events have been ascribed to an increase in aldosterone and hypertension in spite of an increase in HDL-C and a reduction in LDL-C. [2][3][4]6 These unexpected adverse consequences with torcetrapib treatment raised serious concerns about a CETP-based strategy for increasing HDL-C levels and the drug was discontinued. However, the two remaining drugs in this class-anacetrapib and dalcetrapib-are being pursued, and they are the focus of this editorial.…”

Section: Torcetrapibmentioning

confidence: 99%

Novel Cholesteryl Ester Transfer Protein Inhibitors: Promising Therapy for Dyslipidemia?

Devaraj

Jialal

2011

Metabolic Syndrome and Related Disorders

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High-density lipoprotein therapeutics and cardiovascular prevention

Cited by 25 publications

References 94 publications

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Less known pathophysiological mechanisms of anemia in patients with diabetic nephropathy

Obesity and altered glucose metabolism impact HDL composition in CETP transgenic mice: a role for ovarian hormones

Novel Cholesteryl Ester Transfer Protein Inhibitors: Promising Therapy for Dyslipidemia?

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