Building an institutional K awardee program at UC Davis through utilization of CTSA resources.

NIH offers multiple mentored career development award mechanisms. By building on the UC Davis Clinical and Translational Science Center (CTSC) from its initial NIH funding in 2006, we created an institution-wide K scholar resource. We investigated subsequent NIH funding for K scholars and to what extent CTSC research resources were used.

Lp(a)-Associated Oxidized Phospholipids in Healthy Black and White Participants in Relation to apo(a) Size, Age, and Family Structure.

Background Lp(a) (lipoprotein(a)) is the major lipoprotein carrier of oxidized phospholipids (OxPL) and this function mediates Lp(a) atherogenicity. However, the relationship between OxPL, Lp(a), and genetic and biological characteristics remains poorly understood. We assessed the relationship between Lp(a)-bound OxPL, apolipoprotein(a) (apo(a)) size, age, and family structure in 2 racial groups.

PCSK9 in African Americans and Caucasians in Relation to Lp(a) Level, Apo(a) Size and Heritability.

Context: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces lipoprotein(a) [Lp(a)] levels, but the association of PCSK9 with Lp(a) level and its major determinant, apolipoprotein(a) [apo(a)] size, is not fully understood.

Objective: To assess the relationship between PCSK9, Lp(a) level, apo(a) size, age, and ethnicity/race.

Design: Cross-sectional.

Heritability of apolipoprotein (a) traits in two-generational African-American and Caucasian families.

Heritability of allele, apo(a) isoform sizes, and isoform-associated lipoprotein(a) [Lp(a)] levels was studied in 82 Caucasian and African-American families with two parents and two children (age: 6-74 years). We determined: ) Lp(a) levels; ) allele sizes; ) apo(a) isoform sizes; and ) isoform-specific apo(a) levels (ISLs), the amount of Lp(a) carried by an individual apo(a) isoform. Trait heritability was estimated by mid-parent-offspring analysis.

Effect of antiretroviral therapy on allele-associated Lp(a) level in women with HIV in the Women's Interagency HIV Study.

We previously demonstrated an association between lipoprotein (a) [Lp(a)] levels and atherosclerosis in human immunodeficiency virus (HIV)-seropositive women. The effects of antiretroviral therapy (ART) on Lp(a) levels in relation to apo(a) size polymorphism remain unclear. ART effects on allele-specific apo(a) level (ASL), an Lp(a) level associated with individual apo(a) alleles within each allele-pair, were determined in 126 HIV-seropositive women.

The roles of apo(a) size, phenotype, and dominance pattern in PCSK9-inhibition-induced reduction in Lp(a) with alirocumab.

An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials.

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study.

Objective: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear.

Lipid Lowering with Soluble Dietary Fiber.

Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods.

Lipoprotein (a): impact by ethnicity and environmental and medical conditions.

Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan.

Combined High-Density Lipoprotein Proteomic and Glycomic Profiles in Patients at Risk for Coronary Artery Disease.

Objectives: To test whether recently developed methods for comprehensive profiling of the high-density lipoprotein (HDL) glycome combined with the HDL proteome can distinguish individuals with coronary artery disease (CAD) from those without.

Methods: Twenty subjects at risk for CAD, who underwent diagnostic coronary arteriography, were analyzed. Ten subjects had CAD, and ten did not.

Lipoprotein(a) and apolipoprotein(a) in polycystic ovary syndrome.

Objective: Levels of lipoprotein(a), Lp(a), an independent risk factor for cardiovascular disease (CVD), are affected by sex hormones. Women with polycystic ovary syndrome (PCOS) have elevated androgen levels and are at increased CVD risk. We investigated the impact of PCOS-related hormonal imbalance on Lp(a) levels in relation to apo(a) gene size polymorphism, a major regulator of Lp(a) level.

Attenuated age-impact on systemic inflammatory markers in the presence of a metabolic burden.

Background: The overall burden of chronic disease, inflammation and cardiovascular risk increases with age. Whether the relationship between age and inflammation is impacted by presence of an adverse metabolic burden is not known.

Methods: We determined inflammatory markers in humans (336 Caucasians and 224 African Americans) and in mice, representing a spectrum of age, weight and metabolic burden.

Diverging trajectory patterns of systemic versus vascular inflammation over age in healthy Caucasians and African-Americans.

Objective: Age and inflammation are risk factors for cardiovascular disease but the impact of inflammation on cardiovascular risk across the lifespan is not understood. We investigated whether an inflammatory burden is modulated by age in healthy subjects.

Methods: Caucasian and African-American families were recruited from the general population (age range: 6-74 years, n = 267).

Rhesus monkey (Macaca mulatta) lipoprotein(a) and apolipoprotein(a): high frequency of small size apolipoprotein(a) isoforms.

Background: Levels of lipoprotein(a), Lp(a), a genetically regulated independent cardiovascular risk factor present in humans and Old World monkeys, are impacted by the apolipoprotein(a), apo(a), gene. Allele-specific apo(a) levels, taking both the apo(a) genotypic and phenotypic characteristics into account, are useful markers to determine atherosclerotic cardiovascular risk.

Methods: We determined (i) the genetic variability of apo(a), (ii) Lp(a) levels, and (iii) allele-specific apo(a) levels in rhesus monkeys (n = 95).

Significant associations between lipoprotein(a) and corrected apolipoprotein B-100 levels in African-Americans.

Objectives: Lipoprotein(a), Lp(a), represents an apolipoprotein (apo) B-carrying lipoprotein, yet the relationship between Lp(a) and apoB levels has not been fully explored.

Methods: We addressed the relationship between Lp(a) and apoB-containing lipoprotein levels in 336 Caucasians and 224 African-Americans. Our approach takes unique molecular properties of Lp(a) as well as contribution of Lp(a) to the levels of these lipoproteins into account.

HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels.

Objective: Mechanisms underlying the cardiovascular risk of lipoprotein(a) are poorly understood. We investigated the relationship of apolipoprotein(a) (apo(a)) size, lipoprotein(a), and allele-specific apo(a) levels with HIV disease activity parameters in a biethnic population.

Methods And Results: Lipoprotein(a) and allele-specific apo(a) levels were determined in 139 white and 168 black HIV-positive patients.

Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk.

Objective: Apolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD.

Differential associations of serum amyloid A and pentraxin-3 with allele-specific lipoprotein(a) levels in African Americans and Caucasians.

Lipoprotein(a) [Lp(a)] is a cardiovascular disease (CVD) risk factor, where inflammation impacts levels differentially across ethnicity. We investigated the effect of systemic [serum amyloid A (SAA)] and vascular [pentraxin-3 (PTX-3)] inflammation on Lp(a) levels across different apolipoprotein(a) [apo(a)] sizes in a biethnic population. Lp(a) and allele-specific apo(a) levels, apo(a) sizes, SAA, and PTX-3 levels were determined in 336 Caucasians and 224 African Americans.

Lipoprotein(a): genotype-phenotype relationship and impact on atherogenic risk.

In 2010, more than 45 years after the initial discovery of lipoprotein(a) [Lp(a)] by Kare Berg, an European Atherosclerosis Society Consensus Panel recommended screening for elevated Lp(a) in people at moderate to high risk of atherosclerotic cardiovascular disease (CVD). This recommendation was based on extensive epidemiological findings demonstrating a significant association between elevated plasma Lp(a) levels and coronary heart disease, myocardial infarction, and stroke. In addition to those patients considered to be at moderate to high risk of heart disease, statin-treated patients with recurrent heart disease were also identified as targeted for screening of elevated Lp(a) levels.

Age as a modulator of inflammatory cardiovascular risk factors.

Objective: Levels of acute phase reactants are affected by age. The extent to which cardiovascular risk associated with aging is due to an increase in the inflammatory burden is not known. We assessed the relationship with age of inflammatory markers, representing (1) systemic (C-reactive protein, fibrinogen, and serum amyloid-A) and (2) vascular (lipoprotein-associated phospholipase A(2) and pentraxin-3) inflammation.

Enigmatic role of lipoprotein(a) in cardiovascular disease.

Lipoprotein (a), [Lp(a)] has many properties in common with low-density lipoprotein, (LDL) but contains a unique protein apolipoprotein(a), linked to apolipoprotein B-100 by a single disulfide bond. There is a substantial size heterogeneity of apo(a), and generally smaller apo(a) sizes tend to correspond to higher plasma Lp(a) levels, but this relation is far from linear, underscoring the importance to assess allele-specific apo(a) levels. The presence of apo(a), a highly charged, carbohydrate-rich, hydrophilic protein may obscure key features of the LDL moiety and offer opportunities for binding to vessel wall elements.

Usefulness of apolipoprotein B/apolipoprotein A-I ratio to predict coronary artery disease independent of the metabolic syndrome in African Americans.

Studies have demonstrated that the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio predicts cardiovascular risk better than any of the cholesterol indexes. A number of factors that define the metabolic syndrome (MS) differ across African-American and European-American ethnicities. We assessed the relation of the apoB/apoA-I ratio to MS and coronary artery disease (CAD) in 224 African Americans and 304 European Americans.