TRIB1 is a positive regulator of hepatocyte nuclear factor 4-alpha.

The TRIB1 locus has been linked to both cardiovascular disease and hepatic steatosis. Recent efforts have revealed TRIB1 to be a major regulator of liver function, largely, but not exclusively, via CEBPA degradation. We recently uncovered a functional interaction between TRIB1 and HNF4A, another key regulator of hepatic function, whose molecular underpinnings remained to be clarified.

TRIB1 Is Regulated Post-Transcriptionally by Proteasomal and Non-Proteasomal Pathways.

The TRIB1 gene has been associated with multiple malignancies, plasma triglycerides and coronary artery disease (CAD). Despite the clinical significance of this pseudo-kinase, there is little information on the regulation of TRIB1. Previous studies reported TRIB1 mRNA to be unstable, hinting that TRIB1 might be subject to post-transcriptional regulation.

Functional Analysis of a Novel Genome-Wide Association Study Signal in SMAD3 That Confers Protection From Coronary Artery Disease.

Objective: A recent genome-wide association study meta-analysis identified an intronic single nucleotide polymorphism in SMAD3, rs56062135C>T, the minor allele (T) which associates with protection from coronary artery disease. Relevant to atherosclerosis, SMAD3 is a key contributor to transforming growth factor-β pathway signaling. Here, we seek to identify ≥1 causal coronary artery disease-associated single nucleotide polymorphisms at the SMAD3 locus and characterize mechanisms whereby the risk allele(s) contribute to coronary artery disease risk.

Role of Tribbles Pseudokinase 1 (TRIB1) in human hepatocyte metabolism.

Genome-wide association studies for plasma triglycerides and hepatic steatosis identified a risk locus on chromosome 8q24 close to the TRIB1 gene, encoding Tribbles Pseudokinase 1 (TRIB1). In previous studies conducted in murine models, hepatic over-expression of Trib1 was shown to increase fatty acid oxidation and decrease triglyceride synthesis whereas Trib1 knockdown mice exhibited hypertriglyceridemia. Here we have examined the impact of TRIB1 suppression in human and mouse hepatocytes.

Functional interaction between COL4A1/COL4A2 and SMAD3 risk loci for coronary artery disease.

Objective: The COL4A1/COL4A2 region on chromosome 13q34 is a highly replicated locus for coronary artery disease (CAD). In the normal arterial wall, type IV collagen acts to inhibit smooth muscle cell proliferation. Its production is in part a function of TGFβ signaling, but the specific regulatory mechanisms, especially in humans, have not been defined.

Go protein subunit Goα and the secretory process of the natriuretic peptide hormones ANF and BNP.

Expression of the G protein subunit Goα has been shown to be prominent in the atria of the rat heart and to be significantly associated with atrial natriuretic factor (ANF)-containing atrial-specific secretory granules by immunocytochemistry. In addition, differential expression profile analysis using oligonucleotide arrays has shown that the Goα isoform 1 (Goα1) is 2.3-fold more abundant in the atria than it is in the ventricles.

Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease.

Background: The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid-associated single nucleotide polymorphisms (SNPs), identified by genome-wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits.

ERK1/2 regulates hepatocyte Trib1 in response to mitochondrial dysfunction.

The TRIB1 locus (8q24.13) is a novel locus identified and replicated by several genome-wide association studies for associations with plasma triglycerides, apolipoprotein B and coronary artery disease. The TRIB1 protein product, tribbles-like protein 1 (Trib1), regulates MAPK activity.

Characterization of a long-acting recombinant human serum albumin-atrial natriuretic factor (ANF) expressed in Pichia pastoris.

The cardiac hormone atrial natriuretic factor (ANF) combines pharmacological properties of drugs used to treat essential hypertension (EH), congestive heart failure (CHF) and acute myocardial infarction (AMI). Treatment of CHF or AMI patients with an intravenous (iv) infusion of the circulating form of ANF (ANF(99-126)) produces significant clinical improvement. The short half-life (5 min) and peptide nature of ANF impose logistic restrictions for chronic administration.

Cardiac hormones ANF and BNP modulate proliferation in the unidirectional mixed lymphocyte reaction.

Background: Previous investigations have shown that the plasma levels of the cardiac hormone brain natriuretic peptide (BNP) increase during acute cardiac allograft rejection as diagnosed by endomyocardial biopsy. Successful immunosuppressant treatment decreased plasma BNP levels, suggesting a role for BNP in transplantation immunity. We tested a possible immunomodulatory effect of the natriuretic peptides (NPs) BNP, atrial natriuretic factor (ANF), and C-type NP (CNP) using the unidirectional mixed lymphocyte reaction (MLR).