The influence of glucocorticoids on lipid and lipoprotein metabolism and atherosclerosis

Ross, Ian Louis; Marais, A. David

doi:10.7196/samj.7979

Cited by 27 publications

(14 citation statements)

References 19 publications

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“…Corticosteroid treatment increases plasma LDL levels in humans. 35,36 The present study also found that daily inhalation of budesonide increased plasma LDL and total cholesterol (Table 4). A recent randomized control study demonstrated a role of ketotifen in reducing plasma cholesterol and LDL and increased plasma HDL.…”

Section: Resultssupporting

confidence: 77%

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

Liu

Wang

Liao

et al. 2016

Translational Research

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Inflammation drives asthma and atherosclerosis. Clinical studies suggest that asthmatic patients have a high risk of atherosclerosis. Yet this hypothesis remains uncertain, given that Th2 imbalance causes asthma whereas Th1 immunity promotes atherosclerosis. In this study, chronic allergic lung inflammation (ALI) was induced in mice by ovalbumin sensitization and challenge. Acute ALI was induced in mice by ovalbumin and aluminum sensitization and ovalbumin challenge. Atherosclerosis was produced in apolipoprotein E-deficient (Apoe−/−) mice with a Western diet. When chronic ALI and atherosclerosis were produced simultaneously, ALI increased atherosclerotic lesion size, lesion inflammatory cell content, elastin fragmentation, smooth muscle cell (SMC) loss, lesion cell proliferation, and apoptosis. Production of acute ALI before atherogenesis did not affect lesion size, but increased atherosclerotic lesion CD4+ T cells, lesion SMC loss, angiogenesis, and apoptosis. Production of acute ALI after atherogenesis also did not change atherosclerotic lesion area, but increased lesion elastin fragmentation, cell proliferation, and apoptosis. In mice with chronic ALI and diet-induced atherosclerosis, daily inhalation of a mast cell inhibitor or corticosteroid significantly reduced atherosclerotic lesion T-cell and mast cell contents, SMC loss, angiogenesis, and cell proliferation and apoptosis, although these drugs did not affect lesion area, compared with those that received vehicle treatment. In conclusion, both chronic and acute ALI promote atherogenesis or aortic lesion pathology, regardless whether ALI occurred before, after, or at the same time as atherogenesis. Anti-asthmatic medication can efficiently mitigate atherosclerotic lesion pathology.

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Section: Resultssupporting

confidence: 77%

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

Liu

Wang

Liao

et al. 2016

Translational Research

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“…While the exact mechanism by which Dex treatment alters HDL levels is not well known, in a rat model, Dex reduced the activity of LPL and increased the activity of lecithin:cholesterol acyltransferase (LCAT), an enzyme which can convert free cholesterol to cholesteryl ester, which then enhances the production of HDL ( Jansen et al, 1992 ). Although the effect of Dex on the lipid profile depends on many factors such as dose and duration, as well as genetic variations and environmental factors ( Ross and Marais, 2014 ), in this study, the dose frequency and length of exposure to Dex were sufficient to maintain both total cholesterol and HDL levels within the normal range, but increase the TG and decrease the LDL levels significantly.…”

Section: Discussionmentioning

confidence: 63%

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats

et al. 2018

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Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.

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“…[ 32 – 34 ] Some apparent unfavorable changes have been reported in regard to LDL-C and vLDL-C metabolism with the utilization of glucocorticoids by Ross and Marais. [ 35 ] Dexamethasone, as a routine premedication, is given to BC patients who received paclitaxel to avoid hypersensitivity reactions and vomiting. [ 36 ] In the present study, we demonstrated that FEC regimen had less side effects on lipid profiles and the incidence of newly dyslipidemia after chemotherapy was also lowest in patients receiving FEC than that of the other chemotherapy regimens.…”

Section: Discussionmentioning

confidence: 99%

Adjuvant chemotherapy-associated lipid changes in breast cancer patients

Wang

Tan

et al. 2020

Medicine

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Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid. We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); epirubicin and cyclophosphamide followed by paclitaxel (EC-T); cyclophosphamide and paclitaxel (TC); and fluorouracil, cyclophosphamide, and epirubicin (FEC). The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above ( P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG ( P = .006), high-density lipoprotein (HDL-C) ( P < .001), and LDL-C ( P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group ( P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients ( P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG ( P = .004) and a low level of HDL-C ( P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 ( P < .001; P = .036; P = .012; P = .048, respectively). BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.

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The influence of glucocorticoids on lipid and lipoprotein metabolism and atherosclerosis

Cited by 27 publications

References 19 publications

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

Allergic lung inflammation promotes atherosclerosis in apolipoprotein E-deficient mice

Metabolomics Based Profiling of Dexamethasone Side Effects in Rats

Adjuvant chemotherapy-associated lipid changes in breast cancer patients

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