Alan Daugherty
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View article: Angiotensin II Induces Abdominal Aortic Branch Aneurysms in <i>Fibrillin-1</i> <sup> <i>C1041G/+</i> </sup> Mice
Angiotensin II Induces Abdominal Aortic Branch Aneurysms in <i>Fibrillin-1</i> <sup> <i>C1041G/+</i> </sup> Mice Open
Background Mice harboring a missense variant (C1041G) of fibrillin-1 ( Fbn1 ) have been used extensively for aortopathy research, but do not mimic all facets of the human disease. The role of increased angiotensin II (AngII) or blood press…
View article: Cardiac Hemorrhage Precedes Hypertension-induced Fibrosis in Plasminogen Activator Inhibitor-1 Deficient Mice
Cardiac Hemorrhage Precedes Hypertension-induced Fibrosis in Plasminogen Activator Inhibitor-1 Deficient Mice Open
Aims Plasminogen activator inhibitor-1 (PAI-1) regulates plasmin-mediated proteolysis, thereby influencing vascular stability and tissue remodeling. Angiotensin II (AngII) induces an increase of PAI-1 during the development of ascending th…
View article: β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice
β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice Open
Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Cilostazol, a phosphodiesterase (PDE) 3 inhibitor, and sildenafil, a PDE5 inhibitor, have been used clinically for peripheral arterial disease…
View article: Reporting Sex and Sex Differences in Preclinical Studies
Reporting Sex and Sex Differences in Preclinical Studies Open
ATVB publishes research work that advances scientific fields in a rigorous and reproducible manner. We have implemented multiple approaches to follow the National Institutes of Health guidelines for rigor and reproducibility. In 2013, ATVB…
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: Metformin Does Not Attenuate Angiotensin II-Induced Aortic Aneurysms in Low-Density Lipoprotein Receptor Deficient Mice
Metformin Does Not Attenuate Angiotensin II-Induced Aortic Aneurysms in Low-Density Lipoprotein Receptor Deficient Mice Open
Background Metformin, a biguanide antihyperglycemic agent, prevents angiotensin II (AngII)-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient (ApoE−/−) mice. Low-density lipoprotein receptor-deficient (LDLR−/−) mice …
View article: Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations
Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations Open
Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the…
View article: Hepatocyte-specific angiotensinogen deficiency inhibits Western diet-induced liver steatosis with suppression of cell division in mice
Hepatocyte-specific angiotensinogen deficiency inhibits Western diet-induced liver steatosis with suppression of cell division in mice Open
Liver steatosis is a common cause of chronic liver disease. To investigate the molecular basis of hepatic steatosis, low-density lipoprotein receptor-deficient (LDLR -/-) mice were fed a Western diet (WD, 42% of calories from fat) for 5, 1…
View article: Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm
Endothelium- and Fibroblast-Derived C-Type Natriuretic Peptide Prevents the Development and Progression of Aortic Aneurysm Open
BACKGROUND: Thoracic (TAA) and abdominal (AAA) aortic aneurysm are life-threatening diseases characterized by dilation, inflammation, and structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natr…
View article: β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice
β-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice Open
Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide concentrations. Recent studies report the influences of cilostazol, a PDE3 …
View article: Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models
Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models Open
There is a recent dramatic increase in research on thoracic aortic diseases that includes aneurysms, dissections, and rupture. Experimental studies predominantly use mice in which aortopathy is induced by chemical interventions, genetic ma…
View article: Smooth Muscle Cells and Fibroblasts in the Proximal Thoracic Aorta Exhibit Minor Differences Between Embryonic Origins in Angiotensin II-driven Transcriptional Alterations
Smooth Muscle Cells and Fibroblasts in the Proximal Thoracic Aorta Exhibit Minor Differences Between Embryonic Origins in Angiotensin II-driven Transcriptional Alterations Open
Background Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the proximal region of the thoracic aorta being susceptible. Smooth muscle cells (SMCs) and selected fibroblasts in this region…
View article: Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet
Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet Open
BACKGROUND: Pharmacological inhibition of megalin (also known as LRP2 [low-density lipoprotein receptor-related protein-2]) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (…
View article: Platelets are Protective in Early Abdominal Aortic Aneurysm Formation
Platelets are Protective in Early Abdominal Aortic Aneurysm Formation Open
Background Abdominal aortic aneurysm (AAA) is a disease associated with the pathophysiologic degradation of the tunica media resulting in aortic dilatation, systemic inflammation, and dysregulated hemostasis. Beyond role its role in initia…
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: Attenuation of Atherosclerosis with PAR4 Deficiency: Differential Platelet Outcomes in apoE<sup>-/-</sup>vs. Ldlr<sup>-/-</sup>Mice
Attenuation of Atherosclerosis with PAR4 Deficiency: Differential Platelet Outcomes in apoE<sup>-/-</sup>vs. Ldlr<sup>-/-</sup>Mice Open
Objective Cardiovascular disease (CVD) is a significant burden globally and, despite current therapeutics, remains the leading cause of death. Platelet inhibitors are of interest in CVD treatment to reduce thrombus formation post-plaque ru…
View article: Myeloid-Specific Thrombospondin-1 Deficiency Exacerbates Aortic Rupture via Broad Suppression of Extracellular Matrix Proteins
Myeloid-Specific Thrombospondin-1 Deficiency Exacerbates Aortic Rupture via Broad Suppression of Extracellular Matrix Proteins Open
Rationale Rupture of abdominal aortic aneurysms (AAA) is associated with high mortality. However, the precise molecular and cellular drivers of AAA rupture remain elusive. Our prior study showed that global and myeloid-specific deletion of…
View article: β-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice
β-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice Open
BACKGROUND: β-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to ge…
View article: Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet
Renal Proximal Tubule Cell-specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed Western Diet Open
Background Pharmacological inhibition of megalin (also known as low-density lipoprotein receptor-related protein 2: LRP2) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PT…
View article: Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases
Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases Open
AGT (angiotensinogen) is the unique precursor for the generation of all the peptides of the renin-angiotensin system, but it has received relatively scant attention compared to many other renin-angiotensin system components. Focus on AGT h…
View article: β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice
β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice Open
BACKGROUND β-aminopropionitrile (BAPN) is a pharmacological inhibitor of lysyl oxidase and lysyl oxidase-like proteins. Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generat…
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: Manipulation of components of the renin angiotensin system in renal proximal tubules fails to alter atherosclerosis in hypercholesterolemic mice
Manipulation of components of the renin angiotensin system in renal proximal tubules fails to alter atherosclerosis in hypercholesterolemic mice Open
Background and objective Whole body manipulation of the renin-angiotensin system (RAS) consistently exerts profound effects on experimental atherosclerosis development. A deficit in the literature has been a lack of attention to the effect…
View article: Functional Exploration of Conserved Sequences in the Distal Face of Angiotensinogen—Brief Report
Functional Exploration of Conserved Sequences in the Distal Face of Angiotensinogen—Brief Report Open
BACKGROUND: Angiotensinogen (AGT) is an essential component in the renin-angiotensin system. AGT has highly conserved sequences in the loop and β-sheet regions among species; however, their functions have not been studied. METHODS: Adeno-a…
View article: Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice Open
Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investi…