Finasteride Reduces Total Cholesterol in LDLR-Deficient Mice

Abstract Objectives Androgen imbalance is associated with cardiovascular disease risk but the exact impact on lipid and glucose profile is unknown. Finasteride (FIN) prevents the conversion of testosterone to its active metabolite dihydrotestosterone (DHT) by inhibiting the type II 5alpha-reductase. Our objective is to examine the impact of FIN on cardiovascular disease risk. We hypothesize that FIN delays the progression of atherosclerosis by ameliorating hyperglycemia and dyslipidemia. Methods We used the low-density lipoprotein receptor (LDLR)-deficient (Ldlr−/−) mouse model as a widely regarded model of atherosclerotic plaque development in rodents. Four-week-old male mice (n = 9–15/group) were fed a Western-diet containing 41% fat +0.3% cholesterol with increasing doses of FIN (10 mg/kg, 100 mg/kg, and 1000 mg/kg diet) for 12 weeks. Littermates fed Western-diet without FIN were used as a control group. A week before tissue harvest, mice were subjected to a glucose tolerance test (GTT). At the end of the experiment, mice were sacrificed, and their tissue and body weights were analyzed. A total cholesterol assay was performed at 0, 4, 8, and 12 weeks. Results We examined prostate size, whose growth is DHT dependent, as an indicator of the effect of finasteride in our experimental model. We observed a dose-dependent effect of FIN on prostate size for all the doses (P < .0001), indicating FIN had a physiological impact on these mice. No changes in food intake or circulating transaminase levels were observed, discarding any evidence of food intolerability or hepatic toxicity. FIN did not alter GTT among experimental groups or any other biometric parameter. However, we observed a significant reduction in body weight gain in the high dose group (P = .0027) in comparison to the other experimental groups. Total cholesterol levels at the time of the sacrifice were significantly reduced in the high dose group (P < .0001) in comparison to the other experimental groups. Future experiments will include atherosclerotic plaque characterization of both size and composition. Conclusions Our findings suggest that a high dose of FIN is associated with a reduction of total plasma cholesterol and body weight in Ldlr−/− mice. Funding Sources USDA multistate hatch project (W4002)

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Effect of Mixed Nut Consumption on Cardiovascular Disease Risk Factors in Overweight and Obese Adults (OR19-05-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz046.or19-05-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Nazanin Abbaspour ◽

Traci Roberts ◽

Shirin Hooshmand ◽

Mark Kern ◽

Mee Young Hong

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Body Weight ◽

Liver Function ◽

Antioxidant Capacity ◽

Total Cholesterol ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cardiovascular Disease Risk Factors ◽

Snack Food

Abstract Objectives Emerging research indicates that nuts are a source of compounds that promote cardioprotective benefits. However, most studies have assessed the effect of single nuts rather than a mixture containing a variety of nuts. Therefore, the objective of this study is to examine the effect of mixed nuts on cardiovascular disease risk factors including inflammation, glucose, insulin, antioxidant capacity, and liver function. Methods In an 8-week randomized controlled trial, 48 participants (19 female and 29 male, 18–54 years) were equally divided into groups that consumed isocaloric (250 kcal) amounts of pretzels (69g) or mixed nuts (42.5g) for 8 weeks. Serum lipids, inflammatory biomarkers, oxidative stress, antioxidant capacity, antioxidant enzymes, and markers of liver function were measured at baseline and 4 weeks and 8 weeks after intervention. Results Significant decreases were detected for body weight (P = 0.013) and BMI (P = 0.022), but only within the nut group. Nut consumption reduced glucose (P = 0.040) and insulin (P = 0.032) concentrations after 4 and 8 weeks, respectively; whereas, pretzel intake increased triglycerides (P = 0.048) between week 4 to week 8. While total cholesterol did not change, HDL-C (P = 0.044) dropped and LDL-C (P = 0.038) increased from baseline to week 4 of pretzel consumption with no significant changes in the nut group. Among liver function biomarkers, alkaline phosphatase exhibited a reducing trend from baseline to week 8 of nut ingestion and lactate dehydrogenase decreased significantly from baseline and week 4 to week 8 (P < 0.01), while it increased within the pretzel group at week 8 compared to baseline (P = 0.018). Conclusions Our results suggest that the incorporation of mixed-nuts into the diet improves body weight, some liver and cardiac functions, and maintains total cholesterol, triglyceride, HDL-C, and LDL-C levels in comparison to a refined snack food. Future research should determine whether nuts impact cardiovascular disease outcomes. Funding Sources American Heart Association (16GRNT31360007).

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Cardiovascular Disease Risk Factors: How Relevant in African Men With Prostate Cancer Receiving Androgen-Deprivation Therapy?

Journal of Global Oncology ◽

10.1200/jgo.2015.002790 ◽

2017 ◽

Vol 3 (1) ◽

pp. 7-14

Author(s):

Okon Ekwere Essien ◽

Iya Eze Bassey ◽

Rebecca Mtaku Gali ◽

Alphonsus Ekpe Udoh ◽

Uwem Okon Akpan ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Waist Circumference ◽

Total Cholesterol ◽

Ldl Cholesterol ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Treatment Naïve

Purpose Cardiovascular disease risk factors have been associated with androgen-deprivation therapy (ADT) in white and Hispanic populations. It is therefore relevant to determine if there exists a relationship between these parameters in the African population. Patients and Methods The design of the study was cross sectional. Prostate-specific antigen concentration, waist circumference, body mass index (BMI), lipid profile, glucose level, and insulin level were determined in 153 patients with prostate cancer and 80 controls. The patients with prostate cancer were divided into subgroups of treatment-naïve patients and those receiving ADT. Results Mean total cholesterol ( P = .010), LDL cholesterol ( P = .021), BMI ( P = .001), and waist circumference ( P = .029) values were significantly higher in patients treated with ADT when compared with treatment-naïve patients. In patients treated with ADT for up to 1 year, only mean BMI was significantly higher than in treatment-naïve patients, whereas those treated with ADT for more than 1 year had significantly higher mean BMI, waist circumference, total cholesterol, and LDL cholesterol values when compared with treatment-naïve patients. There were no significant differences in insulin or glucose levels. Those undergoing hormone manipulation after orchiectomy had fewer cardiovascular risk factors compared with those undergoing hormone manipulation alone. Conclusion This study shows that ADT results in elevated total cholesterol, LDL cholesterol, BMI, and waist circumference values, all of which are risk factors of cardiovascular disease. Screening for cardiovascular risk factors should be included in treatment plans for patients with prostate cancer.

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Time-of-day and Meal Size Effects on Clinical Lipid Markers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa739 ◽

2020 ◽

Author(s):

Leilah K Grant ◽

Charles A Czeisler ◽

Steven W Lockley ◽

Shadab A Rahman

Keyword(s):

Cardiovascular Disease ◽

Total Cholesterol ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Density Lipoprotein ◽

Time Of Day ◽

Lipoprotein Cholesterol ◽

Shift Workers ◽

Postprandial Lipid Metabolism ◽

Lipid Panel

Abstract Context Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology. Objective To examine the effects of eating at different times of day on lipid profiles. Design Two 24-hour baseline days with 8 hours of sleep, 3 meals (breakfast, lunch, dinner) and a snack, followed by a 40-hour constant routine (CR) with hourly isocaloric meals. Setting Intensive Physiological Monitoring Unit, Brigham and Women’s Hospital. Participants Twenty-one healthy adults [23.4 ± 2.7 years, 5F] Intervention Forty-hour CR. Main Outcome Measures A standard clinical lipid panel, consisting of total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), was assayed in blood samples collected 4-hourly across ~4 days. Results When participants ate at night, levels of TG were similar to eating during the day, however, these levels at night were reached with consuming approximately half the calories. Additionally, 24-hour levels of TG were 10% higher when meals were consumed hourly across 24 hours compared to consuming a typical 3-meal schedule while awake during the day and sleeping at night. The endogenous circadian rhythms of TG, which peaked at night, were shifted earlier by ~10 hours under baseline conditions, whereas the rhythms in total cholesterol, HDL-C, and LDL-C remained unchanged and peaked in the afternoon. Conclusions The time-of-day dependency on postprandial lipid metabolism, which leads to hypersensitivity in TG responses when eating at night, may underlie the dyslipidemia and elevated cardiovascular disease risk observed in shift workers.

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Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316779 ◽

2021 ◽

Author(s):

Maria J. Iglesias ◽

Larissa D. Kruse ◽

Laura Sanchez-Rivera ◽

Linnea Enge ◽

Philip Dusart ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Body Mass Index ◽

Risk Factor ◽

Total Cholesterol ◽

Body Mass ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cardiovascular Disease Risk Factor ◽

Venous Disease

Objective: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results: We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (n=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles. Conclusions: EC proteins in plasma could reflect vascular health status.

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