BT2 Suppresses Human Monocytic-Endothelial Cell Adhesion, Bone Erosion and Inflammation.

Introduction: Inflammation and bone erosion are processes key to the pathogenesis of rheumatoid arthritis, a systemic autoimmune disease causing progressive disability and pain, impacting around 1.3 million people in the United States alone. However, many patients do not respond sufficiently to existing therapies or benefit is not sustained and alternate therapeutic approaches are lacking.

Relationship of fibroblast growth factor 21 levels with inflammation, lipoproteins and non-alcoholic fatty liver disease.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and atherogenic lipoprotein abnormalities. Previous studies suggest an association of fibroblast growth factor 21 (FGF21) with NAFLD. Therefore, we assessed the association of circulating FGF21 levels with inflammatory markers, lipoprotein profile and NAFLD in the Multi-Ethnic Study of Atherosclerosis (MESA).

The Cholesteryl Ester Transfer Protein Inhibitor, des-Fluoro-Anacetrapib, Prevents Vein Bypass-induced Neointimal Hyperplasia in New Zealand White Rabbits.

Coronary artery bypass grafting is among the most commonly performed of all cardiovascular surgical procedures. However, graft failure due to stenosis reduces the long-term benefit of the intervention. This study asks if elevating plasma high density lipoprotein cholesterol (HDL-C) levels by inhibition of cholesteryl ester transfer protein (CETP) activity with des-fluoro-anacetrapib, an analog of the CETP inhibitor anacetrapib, prevents vein bypass-induced neointimal hyperplasia.

Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis.

Background And Aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline.

Apolipoprotein A-I Protects Against Pregnancy-Induced Insulin Resistance in Rats.

Objective- Insulin resistance and inflammation in pregnancy are risk factors for gestational diabetes mellitus. Increased plasma HDL (high-density lipoprotein) and apo (apolipoprotein) A-I levels have been reported to improve glucose metabolism and inhibit inflammation in animals and humans. This study asks whether increasing plasma apoA-I levels improves insulin sensitivity and reduces inflammation in insulin-resistant pregnant rats.

Apolipoprotein A-I enhances insulin-dependent and insulin-independent glucose uptake by skeletal muscle.

Therapeutic interventions that increase plasma high density lipoprotein (HDL) and apolipoprotein (apo) A-I levels have been reported to reduce plasma glucose levels and attenuate insulin resistance. The present study asks if this is a direct effect of increased glucose uptake by skeletal muscle. Incubation of primary human skeletal muscle cells (HSKMCs) with apoA-I increased insulin-dependent and insulin-independent glucose uptake in a time- and concentration-dependent manner.

Association of elevated circulating fibroblast growth factor 21 levels with prevalent and incident metabolic syndrome: The Multi-Ethnic Study of Atherosclerosis.

Background And Aims: Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. We have investigated the relationship of plasma FGF21 levels with both prevalent and incident metabolic syndrome (MetS) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: 5783 participants from four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American) were included in the cross-sectional analysis.

Role of fibroblast growth factor 21 in gestational diabetes mellitus: A mini-review.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first diagnosis during pregnancy, but not to the level of being diagnostic for diabetes in a nonpregnant adult. In GDM, whole-body insulin-dependent glucose disposal decreases by 40%-60% which necessitates a 200%-250% increase in insulin secretion to maintain normoglycaemia. GDM develops when a pregnant woman does not produce sufficient insulin to compensate for the reduced glucose disposal.

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice.

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans.

Fibroblast growth factor 21 in chronic kidney disease.

The association between fibroblast growth factor 21 (FGF21) and kidney function has been extensively studied in recent years in both animal and human studies. However, the exact functional role of FGF21 in the kidney remains unclear. Previous animal studies have shown that administration of FGF21 ameliorates kidney function, morphological glomerular abnormalities, dyslipidemia, hyperglycemia, insulin resistance, oxidative stress and obesity.

Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein Inhibition.

Objective: Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia.

Approach And Results: New Zealand White rabbits received normal chow or chow supplemented with 0.

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats.

Background: We determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.

Methods: We performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls.

Effects of dietary fat subtypes on glucose homeostasis during pregnancy in rats.

Background: Dietary n-3 and n-6 polyunsaturated fatty acids (PUFAs) have an impact on insulin secretion and sensitivity but whether and how these may be related to maternal glucose homeostasis during pregnancy is unclear.

Methods: Female Wistar rats (240-250 g) were assigned to laboratory CHOW or high fat diets rich in either n-6 (safflower oil; n-6 group) or n-6 + n-3 (safflower oil + fish oil; n-3 group) PUFAs. After 10 days half of the animals in each diet group were inseminated and confirmed pregnant.

Increasing HDL levels by inhibiting cholesteryl ester transfer protein activity in rabbits with hindlimb ischemia is associated with increased angiogenesis.

Background: High density lipoprotein (HDL) infusions increase new blood vessel formation (angiogenesis) in rodents with ischemic injury. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein (CETP) activity increases angiogenesis in New Zealand White (NZW) rabbits with hindlimb ischemia.

Methods And Results: NZW rabbits were maintained for 6weeks on chow or chow supplemented with 0.

Cholesteryl ester transfer protein inhibition enhances endothelial repair and improves endothelial function in the rabbit.

Objective: High-density lipoproteins (HDLs) can potentially protect against atherosclerosis by multiple mechanisms, including enhancement of endothelial repair and improvement of endothelial function. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, enhances endothelial repair and improves endothelial function in New Zealand White rabbits with balloon injury of the abdominal aorta.

Approach And Results: New Zealand White rabbits received chow or chow supplemented with 0.

The relationship between total bilirubin levels and total mortality in older adults: the United States National Health and Nutrition Examination Survey (NHANES) 1999-2004.

Objective: Due to its anti-oxidant and anti-inflammatory properties, bilirubin has been associated with reduced cardiovascular risk. A recent study demonstrated an L-shaped association of pre-treatment total bilirubin levels with total mortality in a statin-treated cohort. We therefore investigated the association of total bilirubin levels with total mortality in a nationally representative sample of older adults from the general population.

Inhibition of arthritis in the Lewis rat by apolipoprotein A-I and reconstituted high-density lipoproteins.

Objective: This study questions whether high-density lipoproteins (HDLs) and apolipoprotein A-I inhibit joint inflammation in streptococcal cell wall peptidoglycan-polysaccharide (PG-PS)-induced arthritis in female Lewis rats.

Approach And Results: Administration of PG-PS to female Lewis rats caused acute joint inflammation after 4 days, followed by remission by day 8. The animals subsequently developed chronic joint inflammation that persisted until euthanasia at day 21.

Trends in C-reactive protein levels in US adults from 1999 to 2010.

C-reactive protein (CRP) is a well-known biomarker of systemic inflammation and cardiovascular disease. We investigated the trends in prevalence of elevated CRP levels (>3.0 mg/L) in a general population of US adults.

Arthritis: its prevalence, risk factors, and association with cardiovascular diseases in the United States, 1999 to 2008.

Objective: Arthritis is associated with cardiovascular diseases (CVDs). However, there are limited epidemiologic studies on arthritis in a national survey study. We therefore investigated the prevalence of self-reported arthritis and its association with CVDs.

High-density lipoproteins inhibit vascular endothelial inflammation by increasing 3β-hydroxysteroid-Δ24 reductase expression and inducing heme oxygenase-1.

Rationale: Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high-density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular inflammation by increasing 3β-hydroxysteroid-Δ24 reductase (DHCR24) expression.

Objective: To determine whether the lipid-free apoA-I-mediated and (A-I)rHDL-mediated increase in DHCR24 expression induces the cytoprotective and potentially cardioprotective enzyme, heme oxygenase-1 (HO-1).

Methods And Results: In vivo: A single intravenous infusion of lipid-free apoA-I (8 mg/kg) administered 24 hours before inserting a nonocclusive periarterial carotid collar into New Zealand White rabbits decreased collar-induced endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, reduced intima/media neutrophil infiltration, and increased DHCR24 and HO-1 mRNA levels.

Niacin inhibits vascular inflammation via the induction of heme oxygenase-1.

Background: Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathological conditions such as atherosclerotic vascular disease and inflammation. Niacin is a pleiotropic drug that slows the progression of coronary artery disease and increases serum levels of the HO-1 enzymatic product bilirubin. This study asks if the cardioprotective properties of niacin involve the induction of HO-1.