Joshua W. Knowles
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View article: Changes in Apolipoprotein A1-Associated Proteomic Composition After Pioglitazone Treatment Versus Weight Loss
Changes in Apolipoprotein A1-Associated Proteomic Composition After Pioglitazone Treatment Versus Weight Loss Open
Insulin resistance (IR) contributes to atherogenic dyslipidemia and elevated ASCVD risk. Apolipoprotein A1 (ApoA1)-associated lipoproteins have diverse anti-atherogenic functions, but it is unclear whether IR drives adverse changes in thei…
View article: Successful Rituximab Treatment of GPIHBP1 Autoantibody-Associated Hypertriglyceridemia
Successful Rituximab Treatment of GPIHBP1 Autoantibody-Associated Hypertriglyceridemia Open
GPIHBP1-AAS-associated hypertriglyceridemia should be recognized and can be successfully treated with rituximab.
View article: Genetics of growth rate in induced pluripotent stem cells
Genetics of growth rate in induced pluripotent stem cells Open
Human induced pluripotent stem cells (iPSCs) have transformed biomedical research by enabling the generation of diverse cell types from accessible somatic tissues. However, certain fundamental biological properties, such as the genetic and…
View article: Cardiologists' Perceptions of Cardiogenetic Testing and Management
Cardiologists' Perceptions of Cardiogenetic Testing and Management Open
View article: Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database
Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: the US Family Heart Database Open
Background and Aims Higher levels of lipoprotein(a) drive increasing risk of atherosclerotic cardiovascular disease (ASCVD) in otherwise healthy individuals regardless of sex and race/ethnicity. This study aimed to evaluate whether this is…
View article: Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations
Cross-sectional, interventional, and causal investigation of insulin sensitivity using plasma proteomics in diverse populations Open
Background We previously reported significant correlations between a direct measure of insulin sensitivity (IS) and blood levels of proteins measured using the Proximity Extension Assay (PEA) in two European cohorts. However, protein corre…
View article: Primary Care Providers’ Perspectives on Receiving Tier 1 Genomic Results from a National Study – the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study
Primary Care Providers’ Perspectives on Receiving Tier 1 Genomic Results from a National Study – the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study Open
Background Patients are increasingly obtaining genetic health information and integrating it into their care with the help of their primary care provider (PCP). However, PCPs may not be adequately prepared to effectively utilize genetic re…
View article: Hymecromone Promotes Longevity and Insulin Sensitivity in Mice
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice Open
Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-te…
View article: One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy
One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy Open
Mavacamten is a first-in-class cardiac myosin ATPase inhibitor, approved by the United States Food and Drug Administration for the treatment of hypertrophic cardiomyopathy with obstructive physiology (oHCM). Here, we present the real-world…
View article: A functional genomic framework to elucidate novel causal metabolic dysfunction–associated fatty liver disease genes
A functional genomic framework to elucidate novel causal metabolic dysfunction–associated fatty liver disease genes Open
Background and Aims: Metabolic dysfunction–associated fatty liver disease (MASLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for MASLD have …
View article: Loss of<i>RREB1</i>reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes
Loss of<i>RREB1</i>reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes Open
There are multiple independent genetic signals at the Ras-responsive element binding protein 1 ( RREB1 ) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown t…
View article: X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction
X chromosome dosage drives statin-induced dysglycemia and mitochondrial dysfunction Open
Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired g…
View article: Generation of two familial hypercholesterolemia patient-specific induced pluripotent stem cell lines harboring heterozygous mutations in the LDLR gene
Generation of two familial hypercholesterolemia patient-specific induced pluripotent stem cell lines harboring heterozygous mutations in the LDLR gene Open
View article: Chemerin in Participants with or without Insulin Resistance and Diabetes
Chemerin in Participants with or without Insulin Resistance and Diabetes Open
Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resista…
View article: Epidemiology of Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes Mellitus and Effects of Antiglycemic Therapy on Liver Fibrosis: A Retrospective Study
Epidemiology of Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes Mellitus and Effects of Antiglycemic Therapy on Liver Fibrosis: A Retrospective Study Open
Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a globally prevalent and multifaceted liver disorder, closely linked to metabolic conditions such as obesity, type 2 diabetes mellitus (T2DM), dyslipidemia and hyp…
View article: Generation of two induced pluripotent stem cell lines from healthy patients of African American ancestry
Generation of two induced pluripotent stem cell lines from healthy patients of African American ancestry Open
Stem cells are a resourceful tool for investigating cardiovascular disease in the context of race and gender. Once derived from blood or skin cells, the reprogrammed induced pluripotent stem cells (iPSCs) adopt an embryonic-like pluripoten…
View article: A functional genomic framework to elucidate novel causal non-alcoholic fatty liver disease genes
A functional genomic framework to elucidate novel causal non-alcoholic fatty liver disease genes Open
Background & Aims Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for NAFLD have been hampered by the r…
View article: Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults
Trends of Lipid Concentrations, Awareness, Evaluation, and Treatment in Severe Dyslipidemia in US Adults Open
View article: Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program
Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program Open
Objective The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research r…
View article: Impact of Virtual Interviewing on Cardiovascular Fellowship Applicant Diversity: Insights From 2 Academic Programs
Impact of Virtual Interviewing on Cardiovascular Fellowship Applicant Diversity: Insights From 2 Academic Programs Open
View article: One-Year Real-World Experience with Mavacamten and its Physiologic Effects on Obstructive Hypertrophic Cardiomyopathy
One-Year Real-World Experience with Mavacamten and its Physiologic Effects on Obstructive Hypertrophic Cardiomyopathy Open
We describe real-world use of mavacamten in 50 patients with oHCM. Consistent with EXPLORER-HCM and VALOR-HCM, we report significant improvement in wall thickness, mitral regurgitation, left ventricular outflow tract obstruction and NYHA c…
View article: Lac-Phe mediates the anti-obesity effect of metformin
Lac-Phe mediates the anti-obesity effect of metformin Open
Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformin’s effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological…
View article: Another Use for Polygenic Risk Scores
Another Use for Polygenic Risk Scores Open
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View article: Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study
Introducing return of results in the Million Veteran Program: Design and pilot results of the MVP-ROAR Familial Hypercholesterolemia Study Open
Background As a mega-biobank linked to a national healthcare system, the Million Veteran Program (MVP) can directly improve the health care and health outcomes of participants. Return of genetic research results at this scale presents chal…
View article: Principles for Health Information Collection, Sharing, and Use: A Policy Statement From the American Heart Association
Principles for Health Information Collection, Sharing, and Use: A Policy Statement From the American Heart Association Open
The evolution of the electronic health record, combined with advances in data curation and analytic technologies, increasingly enables data sharing and harmonization. Advances in the analysis of health-related and health-proxy information …
View article: RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts
RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts Open
Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a …
View article: ARO-ANG3, an investigational RNAI therapeutic, decreases serum LDL-cholesterol, apolipoprotein B, and angiopoietin-like protein 3 in patients with homozygous familial hypercholesterolaemia
ARO-ANG3, an investigational RNAI therapeutic, decreases serum LDL-cholesterol, apolipoprotein B, and angiopoietin-like protein 3 in patients with homozygous familial hypercholesterolaemia Open
View article: A single-cell CRISPRi platform for characterizing candidate genes relevant to metabolic disorders in human adipocytes
A single-cell CRISPRi platform for characterizing candidate genes relevant to metabolic disorders in human adipocytes Open
Genomics efforts led to the identification of many genomic loci that are associated with metabolic traits, many of which are tied to adipose tissue function. However, determination of the causal genes, and their mechanism of action in meta…
View article: Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts
Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts Open
View article: Single-cell transcriptome dataset of human and mouse in vitro adipogenesis models
Single-cell transcriptome dataset of human and mouse in vitro adipogenesis models Open