A5024376952- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Hormonal Regulation and Hypertension
- Renin-Angiotensin System Studies
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Connective tissue disorders research
- Infectious Aortic and Vascular Conditions
- Cardiac, Anesthesia and Surgical Outcomes
- Cardiovascular Disease and Adiposity
- Receptor Mechanisms and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Hypoxia, and Metabolism
- Apelin-related biomedical research
- Blood Pressure and Hypertension Studies
- Cholesterol and Lipid Metabolism
- Liver Disease Diagnosis and Treatment
- Cardiac Valve Diseases and Treatments
- Adipose Tissue and Metabolism
- Nuclear Receptors and Signaling
- Traumatic Brain Injury and Neurovascular Disturbances
- MicroRNA in disease regulation
- Birth, Development, and Health
- Protease and Inhibitor Mechanisms
- Single-cell and spatial transcriptomics
University of Kentucky
2016-2025
Cardiovascular Research Center
2011-2024
Brigham and Women's Hospital
2015-2024
Harvard University
2013-2024
Merck (Germany)
2024
Czech Academy of Sciences, Institute of Physiology
2022-2023
Peking University
2022
National Health and Family Planning Commission
2022
Army Medical University
2021
Southwest Hospital
2021
Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of wall can lead to dissection, rupture, other life-threatening complications. To improve our understanding ATAA pathogenesis, we aimed comprehensively characterize cellular composition ascending identify molecular alterations in each cell population human tissues. Methods: We performed single-cell RNA sequencing analysis tissues from 11 study participants, including 8 patients with (4...
Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes macrophages, we investigated significance pathogenesis AAD its clinical relevance.
Background— Hypercholesterolemia-induced atherosclerosis is attenuated by either pharmacological antagonism of AT 1 receptors or 1A receptor deficiency. However, the mechanism underlying pronounced responses to angiotensin II (Ang II) has not been determined. We hypothesized that hypercholesterolemia stimulates production peptides provide a rationale for profound effect deficiency on atherogenesis. Methods and Results— Atherosclerotic lesions were analyzed in LDL receptor–deficient mice....
The role of the renin angiotensin system (RAS) in atherosclerosis is complex because involvement multiple peptides and receptors. Renin rate-limiting enzyme production all peptides. To determine effects inhibition on atherosclerosis, we administered novel inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr(-/-)) mice. resulted striking reductions atherosclerotic lesion size both aortic arch root. Subsequent studies demonstrated that cultured macrophages...
Objective— microRNA-155 (miR155) plays a critical role in immunity and macrophage inflammation. We aim to investigate the of miR155 atherogenesis. Approach Results— Quantitative real-time polymerase chain reaction showed that was expressed mouse human atherosclerotic lesions. expression macrophages correlated positively with proinflammatory cytokine expression. Lentivirus-mediated overexpression enhanced their inflammatory response lipopolysaccharide through targeting suppressor signaling-1...
Angiotensin II (AngII) infusion into hypercholesterolemic mice accelerates atherosclerosis and promotes formation of abdominal aortic aneurysms (AAAs). The purpose this study was to define whether AngII interacts with receptors on infiltrating versus resident cells in promoting vascular pathologies.Male LDL receptor -/- mice, that were either AT1a +/+ or -/-, fed a fat enriched diet infused saline AngII. AngII-induced augmentation AAAs ablated mice. Bone marrow transplantation studies...
Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset numerous age-associated diseases, mediate metabolic homeostasis. We have uncovered novel role for mitochondrial sirtuin SIRT4 in regulation hepatic lipid metabolism during changes nutrient availability. show levels decrease liver fasting null mice display increased expression peroxisome proliferator-activated receptor α (PPARα) target genes associated with fatty...
Blockade of excessive Toll-like receptor (TLR) signaling is a therapeutic approach being actively pursued for many inflammatory diseases. Here we report Chinese herb-derived compound, sparstolonin B (SsnB), which selectively blocks TLR2- and TLR4-mediated signaling. SsnB was isolated from herb, Spaganium stoloniferum; its structure determined by NMR spectroscopy x-ray crystallography. effectively inhibited cytokine expression in mouse macrophages induced lipopolysaccharide (LPS, TLR4...
Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was determine whether infection normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation mouse increased angiotensin II (AngII)-induced abdominal aortic aneurysms.In initial study, male C57BL/6 were injected intraperitoneally either empty or (D377Y). AAV at 3 doses and fed saturated fat-enriched diet for 6 weeks. Two...
Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is lack of effective therapy preventing rupture. During AAA formation, pathological vascular remodeling driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays critical role in establishing phenotype. Using single-cell RNA sequencing human tissues, we identified increased JMJD3...
Objective— The renin-angiotensin system contributes to atherosclerotic lesion formation. Angiotensin-converting enzyme 2 (ACE2) catabolizes angiotensin II (Ang II) 1–7 (Ang-(1–7)) limit effects of the system. purpose this study was define role ACE2 in atherosclerosis. Methods and Results— Male Ace2 −/ y mice an low-density lipoprotein receptor–deficient background were fed a high-fat diet for 3 months. deficiency increased area ( +/ , 17±1; 23±2 mm P <0.002). This increase blunted by...
The purpose of this study was to determine whether myeloid differentiation factor 88 (MyD88) and its related Toll-like receptors (TLRs) 2 4 contributed the development angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) atherosclerosis.AngII infused into either apoE(-/-) or LDL receptor (LDLR)(-/-) male mice that were MyD88(+/+) (-/-). MyD88 deficiency profoundly reduced AngII-induced AAAs atherosclerosis in both strains. To define specific TLRs had similar effects, AngII...
Objective— This study determined whether angiotensinogen (AGT) has angiotensin II–independent effects using multiple genetic and pharmacological manipulations. Approach Results— All mice were in low-density lipoprotein receptor −/− background fed a saturated fat–enriched diet. In with floxed alleles neomycin cassette intron 2 of the AGT gene (hypoAGT mice), plasma concentrations >90% lower compared their wild-type littermates. HypoAGT had systolic blood pressure, less atherosclerosis,...