Ryan E. Temel
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View article: Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models
Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models Open
BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and controversial. METHODS: Mendelia…
View article: Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights from Genetic and Experimental Models
Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights from Genetic and Experimental Models Open
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medications. This study integrated genetic, proteomic, and metabolomic data to identify causation between increased triglyceride (TG)-rich lipoprotein…
View article: Association of NOTCH3 With Elastic Fiber Dispersion in the Infrarenal Abdominal Aorta of Cynomolgus Monkeys
Association of NOTCH3 With Elastic Fiber Dispersion in the Infrarenal Abdominal Aorta of Cynomolgus Monkeys Open
BACKGROUND: The regional heterogeneity of vascular components and transcriptomes is an important determinant of aortic biology. This notion has been explored in multiple mouse studies. In the present study, we examined the regional heterog…
View article: Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism
Macrophage angiotensin-converting enzyme reduces atherosclerosis by increasing peroxisome proliferator-activated receptor α and fundamentally changing lipid metabolism Open
Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atheroscler…
View article: Association of NOTCH3 with Elastic Fiber Dispersion in the Infrarenal Abdominal Aorta of Cynomolgus Monkeys
Association of NOTCH3 with Elastic Fiber Dispersion in the Infrarenal Abdominal Aorta of Cynomolgus Monkeys Open
Background The regional heterogeneity of vascular components and transcriptomes is an important determinant of aortic biology. This notion has been explored in multiple mouse studies. In the present study, we examined the regional heteroge…
View article: Antisense oligonucleotides targeting hepatic angiotensinogen reduce atherosclerosis and liver steatosis in hypercholesterolemic mice
Antisense oligonucleotides targeting hepatic angiotensinogen reduce atherosclerosis and liver steatosis in hypercholesterolemic mice Open
Hepatocyte-derived angiotensinogen (AGT) is the precursor of angiotensin II (AngII). We determined the effects of hepatocyte-specific (N-acetylgalactosamine-conjugated) antisense oligonucleotides targeting AGT (GalNAc AGT ASO) on AngII-med…
View article: ANTISENSE OLIGONUCLEOTIDES TARGETING HEPATIC ANGIOTENSINOGEN DOSE-DEPENDENTLY REDUCE ATHEROSCLEROSIS AND LIVER STEATOSIS IN HYPERCHOLESTEROLEMIC MICE
ANTISENSE OLIGONUCLEOTIDES TARGETING HEPATIC ANGIOTENSINOGEN DOSE-DEPENDENTLY REDUCE ATHEROSCLEROSIS AND LIVER STEATOSIS IN HYPERCHOLESTEROLEMIC MICE Open
Objective: Liver-derived angiotensinogen (AGT) is the substrate from which renin and ACE generate angiotensin (Ang) II. Ang II not only increases blood pressure, but also is a major determinant of atherosclerosis in hypercholesteremic mice…
View article: Renal Angiotensinogen Is Predominantly Liver Derived in Nonhuman Primates
Renal Angiotensinogen Is Predominantly Liver Derived in Nonhuman Primates Open
[Figure: see text].
View article: Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates
Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates Open
The gut microbiome influences nutrient processing as well as host physiology. Plasma lipid levels have been associated with the microbiome, although the underlying mechanisms are largely unknown, and the effects of dietary lipids on the gu…
View article: Renal Angiotensinogen is Predominantly Liver-Derived in Nonhuman Primates
Renal Angiotensinogen is Predominantly Liver-Derived in Nonhuman Primates Open
AGT (Angiotensinogen) is the unique substrate of the renin-angiotensin system. Liver is the primary source of circulating AGT. The present study determined whether hepatocyte-derived AGT regulates renal AGT accumulation by injecting ASO (a…
View article: The prorenin receptor and its soluble form contribute to lipid homeostasis
The prorenin receptor and its soluble form contribute to lipid homeostasis Open
Hepatic PRR and its soluble form, sPRR, contribute to triglyceride and cholesterol homeostasis and hepatic inflammation. Deletion of hepatic PRR decreased triglyceride levels through a PRR-PPARγ-dependent mechanism but increased hepatic ch…
View article: Monocyte tissue factor–dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin
Monocyte tissue factor–dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin Open
Hypercholesterolemia is a major risk factor for atherosclerosis. It also is associated with platelet hyperactivity, which increases morbidity and mortality from cardiovascular disease. However, the mechanisms by which hypercholesterolemia …
View article: SR-BI (Scavenger Receptor BI), Not LDL (Low-Density Lipoprotein) Receptor, Mediates Adrenal Stress Response—Brief Report
SR-BI (Scavenger Receptor BI), Not LDL (Low-Density Lipoprotein) Receptor, Mediates Adrenal Stress Response—Brief Report Open
Objective: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI −/− ) mice failed to generate iGC in stress conditions, suggesting that SR-…
View article: Small molecule inhibition of gut microbial choline trimethylamine lyase activity alters host cholesterol and bile acid metabolism
Small molecule inhibition of gut microbial choline trimethylamine lyase activity alters host cholesterol and bile acid metabolism Open
The gut microbe-dependent metabolite trimethylamine- N-oxide (TMAO) has been strongly associated with cardiovascular mortality, prompting drug discovery efforts to identify points of therapeutic intervention within the microbe-host TMAO pa…
View article: The Prorenin Receptor and its Soluble Form Contribute to Lipid Homeostasis
The Prorenin Receptor and its Soluble Form Contribute to Lipid Homeostasis Open
Obesity is associated with alterations in hepatic lipid metabolism. We previously identified the prorenin receptor (PRR) as a potential contributor to liver steatosis. Therefore, we aimed to determine the relative contribution of PRR and i…
View article: Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice
Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice Open
Objective: Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measur…
View article: Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy
Surface Engineered Polymersomes for Enhanced Modulation of Dendritic Cells During Cardiovascular Immunotherapy Open
The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regul…
View article: XX sex chromosome complement promotes atherosclerosis in mice
XX sex chromosome complement promotes atherosclerosis in mice Open
Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes,…
View article: microRNA-146a-5p association with the cardiometabolic disease risk factor TMAO
microRNA-146a-5p association with the cardiometabolic disease risk factor TMAO Open
Trimethylamine-N-oxide (TMAO), a microbial choline metabolism byproduct that is processed in the liver and excreted into circulation, is associated with increased atherosclerotic lesion formation and cardiovascular disease risk. Genetic re…
View article: Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP
Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP Open
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathw…
View article: Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development
Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development Open
This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic e…
View article: Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a
Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a Open
Rationale: Inflammation is a key contributor to atherosclerosis. MicroRNA-146a (miR-146a) has been identified as a critical brake on proinflammatory nuclear factor κ light chain enhancer of activated B cells signaling in several cell types…