Hepatic Igf1-deficiency protects against atherosclerosis in female mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Tharini Sivasubramaniyam ◽  
Jiaqi Yang ◽  
Evan Pollock ◽  
Joseph Chon ◽  
Stephanie A Schroer ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Essential Role ◽  
Independent Risk Factor ◽  
Atherogenic Diet ◽  
Lipid Homeostasis ◽  
Male And Female ◽  
Subcutaneous Adiposity ◽  
Igf1 Deficiency

Abstract Atherosclerosis is the leading cause of cardiovascular disease (CVD) with distinct sex-specific pathogenic mechanisms that are poorly understood. Aging, a major independent risk factor of atherosclerosis, correlates with a decline in circulating insulin-like growth factor-1 (IGF-1). However, the precise effects of Igf1 on atherosclerosis remain unclear. In the present study, we assessed the essential role of hepatic Igf1, the major source of circulating IGF-1, in atherogenesis. We generated hepatic Igf1-deficient atherosclerosis-prone ApoE null mice (L-Igf1  -/-ApoE  -/-) using the Cre-loxP system driven by the Albumin promoter. Starting at 6 weeks of age, these mice along with littermate controls, separated into male and female groups, were placed on an atherogenic diet for 18-19 weeks. We show that hepatic Igf1-deficiency led to atheroprotection with reduced plaque macrophages in females, without significant effects in males. This protection in atherosclerosis in females was associated with increased subcutaneous adiposity with impaired lipolysis. Moreover, this impaired lipid homeostasis was associated with disrupted adipokine secretion with reduced circulating IL-6 levels. Together, our data show that endogenous hepatic Igf1 plays a sex-specific regulatory role in atherogenesis potentially through athero-promoting effects of adipose tissue-derived IL-6 secretion. These data provide potential novel sex-specific mechanisms in the pathogenesis of atherosclerosis.

scholarly journals Reconstitution in Proteoliposomes of the Recombinant Human Riboflavin Transporter 2 (SLC52A2) Overexpressed in E. coli

2019 ◽  
Vol 20 (18) ◽  
pp. 4416 ◽  
Author(s):  
Lara Console ◽  
Maria Tolomeo ◽  
Matilde Colella ◽  
Maria Barile ◽  
Cesare Indiveri
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Risk Factor ◽  
Biologically Active ◽  
Suitable Model ◽  
Native Protein ◽  
E Coli ◽  
Few Data ◽  
Riboflavin Transport

Background: the SLC52A2 gene encodes for the riboflavin transporter 2 (RFVT2). This transporter is ubiquitously expressed. It mediates the transport of Riboflavin across cell membranes. Riboflavin plays a crucial role in cells since its biologically active forms, FMN and FAD, are essential for the metabolism of carbohydrates, amino acids, and lipids. Mutation of the Riboflavin transporters is a risk factor for anemia, cancer, cardiovascular disease, neurodegeneration. Inborn mutations of SLC52A2 are associated with Brown-Vialetto-van Laere syndrome, a rare neurological disorder characterized by infancy onset. In spite of the important metabolic and physio/pathological role of this transporter few data are available on its function and regulation. Methods: the human recombinant RFVT2 has been overexpressed in E. coli, purified and reconstituted into proteoliposomes in order to characterize its activity following the [3H]Riboflavin transport. Results: the recombinant hRFVT2 showed a Km of 0.26 ± 0.07 µM and was inhibited by lumiflavin, FMN and Mg2+. The Riboflavin uptake was also regulated by Ca2+. The native protein extracted from fibroblast and reconstituted in proteoliposomes also showed inhibition by FMN and lumiflavin. Conclusions: proteoliposomes represent a suitable model to assay the RFVT2 function. It will be useful for screening the mutation of RFVT2.

scholarly journals Anxiety as a risk factor for cardiovascular disease independent of depression: A narrative review of current status and conflicting findings

2021 ◽  
Vol 8 (1) ◽  
pp. 205510292098746
Author(s):  
Håvard R Karlsen ◽  
Florian Matejschek ◽  
Ingvild Saksvik-Lehouillier ◽  
Eva Langvik
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Study Design ◽  
Empirical Support ◽  
Narrative Review ◽  
Current Status ◽  
Depression And Anxiety ◽  
Evidential Support ◽  
Meta Analyses

The aim of this paper is to summarise and evaluate the empirical support for the association between anxiety and cardiovascular disease (CVD) and to address challenges related to method and study design. We review results from meta-analyses and more recent findings on the association of anxiety and the risk of CVD. Depression and anxiety are often listed as psychosocial risk markers of CVD, but the role of anxiety as a risk factor for CVD has not received the same evidential support as the effects of depression. Through a narrative review we identified six meta-analyses as well as 15 recent large studies of anxiety and CVD that we summarise. Some of the conflicting findings may be artefacts of study design or population the sample is drawn from. Researchers should take care to be population specific, measurement specific and outcome specific, and to control for comorbid depression.

scholarly journals Serum uric acid is an independent risk factor for cardiovascular disease and mortality in hypertensive patients

2012 ◽  
Vol 35 (11) ◽  
pp. 1087-1092 ◽  
Author(s):  
Tatsuo Kawai ◽  
Mitsuru Ohishi ◽  
Yasushi Takeya ◽  
Miyuki Onishi ◽  
Norihisa Ito ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Uric Acid ◽  
Risk Factor ◽  
Serum Uric Acid ◽  
Independent Risk Factor ◽  
Hypertensive Patients

Lipids, lipoproteins, and atherogenesis

2011 ◽  
pp. 11-24
Author(s):  
Joanna Gouni-Berthold ◽  
Wilhelm Krone
Keyword(s):  
Risk Factor ◽  
High Density Lipoprotein ◽  
Independent Risk Factor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Apolipoprotein A ◽  
Low Hdl ◽  
Lipids And Lipoproteins

• Lipids and lipoproteins have a central role in the pathogenesis of atherosclerosis. • The concentration of low-density lipoprotein (LDL) is strongly and directly related to risk of atherosclerosis whereas high-density lipoprotein (HDL) is inversly related, low HDL being an independent risk factor. • The role of plasma triglycerides is less well defined. • The ratio of apolipoprotein B (the major apolipoprotein of LDL) to apolipoprotein A-1 (the major apolipoprotein of HDL) is emerging as the best predictor of atherosclerotic risk.

Specific diseases: renal disease

ESC CardioMed ◽  
2018 ◽  
pp. 2670-2673
Author(s):  
Susanna Price
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Kidney Disease ◽  
Renal Disease ◽  
Independent Risk Factor ◽  
Hospital Admissions ◽  
Kidney Injury ◽  
Potential Methods

Chronic kidney disease is a global health burden, with an estimated prevalence of 11–13%, with the majority of patients diagnosed as stage 3, and is an independent risk factor for cardiovascular disease. The incidence of acute kidney injury is increasing, and estimated to be present in one in five acute hospital admissions, and there is a bidirectional relationship between acute and chronic kidney disease. The relevance to the patient with cardiovascular disease relates to increased perioperative risk, as reduced kidney function is an independent risk factor for adverse postoperative cardiovascular outcomes including myocardial infarction, stroke, and progression of heart failure. Furthermore, patients undergoing cardiovascular investigations are at risk of developing acute kidney injury, in particular where iodinated contrast is administered. This chapter reviews the classification of renal disease and its impact on cardiovascular disease, as well as potential methods for reducing the development of contrast-induced acute kidney injury.

scholarly journals Obesity and Cancer: 27-Hydroxycholesterol, the Missing Link

2020 ◽  
Vol 21 (14) ◽  
pp. 4822
Author(s):  
Arvand Asghari ◽  
Michihisa Umetani
Keyword(s):  
United States ◽  
Cardiovascular Disease ◽  
Estrogen Receptor ◽  
Risk Factor ◽  
Cause Of Death ◽  
The United States ◽  
Missing Link ◽  
Receptor Modulator ◽  
Obesity And Cancer

Obesity is currently affecting more than 40% of the Americans, and if it progresses with this rate, soon one out of two Americans will be obese. Obesity is an important risk factor for several disorders including cardiovascular disease, the first cause of death in the United States. Cancer follows as the second deadliest disease, and a link between obesity and cancer has been suggested. However, it is very hard to establish an exact connection between obesity and cancers due to the multifactorial nature of obesity. Hypercholesterolemia is a comorbidity of obesity and also linked to several cancers. Recently a cholesterol metabolite 27-hydroxycholesterol (27HC) was found to be an endogenous selective estrogen receptor modulator (SERM), which opened new doors toward several interesting studies on the role of this molecule in biological disorders. It is speculated that 27HC might be the missing link in the obesity and cancer chain. Here, we explored the effects of 27-hydroxycholesterol on obesity and cancers with a focus on the SERM capacity of 27HC.

scholarly journals Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

2005 ◽  
Vol 51 (11) ◽  
pp. 2067-2073 ◽  
Author(s):  
Daniel T Holmes ◽  
Brian A Schick ◽  
Karin H Humphries ◽  
Jiri Frohlich
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Familial Hypercholesterolemia ◽  
Independent Risk Factor ◽  
Independent Predictor ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic

Abstract Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P <0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P <0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

scholarly journals Is community-acquired pneumonia an independent risk factor for cardiovascular disease?

2011 ◽  
Vol 39 (1) ◽  
pp. 187-196 ◽  
Author(s):  
A. Singanayagam ◽  
A. Singanayagam ◽  
D. H. J. Elder ◽  
J. D. Chalmers
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Community Acquired Pneumonia
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