Try a new search

Format these results:

Searched for:

person:fishee01

in-biosketch:true

Total Results:

431


Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis

Kothari, Vishal; Ho, Tse W W; Cabodevilla, Ainara G; He, Yi; Kramer, Farah; Shimizu-Albergine, Masami; Kanter, Jenny E; Snell-Bergeon, Janet; Fisher, Edward A; Shao, Baohai; Heinecke, Jay W; Wobbrock, Jacob O; Lee, Warren L; Goldberg, Ira J; Vaisar, Tomas; Bornfeldt, Karin E
BACKGROUND/UNASSIGNED:Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.
PMID: 38828596
ISSN: 1524-4571
CID: 5664892

β-Carotene accelerates the resolution of atherosclerosis in mice

Pinos, Ivan; Coronel, Johana; Albakri, Asma'a; Blanco, Amparo; McQueen, Patrick; Molina, Donald; Sim, JaeYoung; Fisher, Edward A; Amengual, Jaume
β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in Bco1-/-
PMID: 38319073
ISSN: 2050-084x
CID: 5632492

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice

Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A.E.; Park, Christopher Y.; Schlamp, Florencia; Heffron, Sean P.; Fisher, Edward A.; Brathwaite, Collin; Ragolia, Louis
Purpose: Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. Methods: A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8 weeks. Results: After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Conclusion: Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk. Graphical Abstract: [Figure not available: see fulltext.].
SCOPUS:85181724544
ISSN: 0960-8923
CID: 5630102

Clonal Expansion in Cardiovascular Pathology

Lin, Alexander; Brittan, Mairi; Baker, Andrew H.; Dimmeler, Stefanie; Fisher, Edward A.; Sluimer, Judith C.; Misra, Ashish
Clonal expansion refers to the proliferation and selection of advantageous "clones" that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited. There is a transpiring pattern of clonal expansion of smooth muscle cells and endothelial cells"”and, in some cases, macrophages"”in numerous cardiovascular diseases irrespective of their differing microenvironments. These findings indirectly suggest the possible existence of stem-like vascular cells which are primed to respond during disease. Subsequent clones may undergo further phenotypic changes to adopt either protective or detrimental roles. By investigating these clone-forming vascular cells, we may be able to harness this inherent clonal nature for future therapeutic intervention. This review comprehensively discusses what is currently known about clonal expansion across the cardiovascular field. Comparisons of the clonal nature of vascular cells in atherosclerosis (including clonal hematopoiesis of indeterminate potential), pulmonary hypertension, aneurysm, blood vessel injury, ischemia- and tumor-induced angiogenesis, and cerebral cavernous malformations are evaluated. Finally, we discuss the potential clinical implications of these findings and propose that proper understanding and specific targeting of these clonal cells may provide unique therapeutic options for the treatment of these cardiovascular conditions.
SCOPUS:85182358386
ISSN: 2452-302x
CID: 5629802

Correction: The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice (Obesity Surgery, (2024), 10.1007/s11695-023-07052-w)

Stevenson, Matthew; Srivastava, Ankita; Nacher, Maria; Hall, Christopher; Palaia, Thomas; Lee, Jenny; Zhao, Chaohui Lisa; Lau, Raymond; Ali, Mohamed A.E.; Park, Christopher Y.; Schlamp, Florencia; Heffron, Sean P.; Fisher, Edward A.; Brathwaite, Collin; Ragolia, Louis
The original article has been corrected to replace the Electronic Supplemental Material.
SCOPUS:85182414932
ISSN: 0960-8923
CID: 5629732

Clonal Expansion in Cardiovascular Pathology

Lin, Alexander; Brittan, Mairi; Baker, Andrew H; Dimmeler, Stefanie; Fisher, Edward A; Sluimer, Judith C; Misra, Ashish
Clonal expansion refers to the proliferation and selection of advantageous "clones" that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited. There is a transpiring pattern of clonal expansion of smooth muscle cells and endothelial cells-and, in some cases, macrophages-in numerous cardiovascular diseases irrespective of their differing microenvironments. These findings indirectly suggest the possible existence of stem-like vascular cells which are primed to respond during disease. Subsequent clones may undergo further phenotypic changes to adopt either protective or detrimental roles. By investigating these clone-forming vascular cells, we may be able to harness this inherent clonal nature for future therapeutic intervention. This review comprehensively discusses what is currently known about clonal expansion across the cardiovascular field. Comparisons of the clonal nature of vascular cells in atherosclerosis (including clonal hematopoiesis of indeterminate potential), pulmonary hypertension, aneurysm, blood vessel injury, ischemia- and tumor-induced angiogenesis, and cerebral cavernous malformations are evaluated. Finally, we discuss the potential clinical implications of these findings and propose that proper understanding and specific targeting of these clonal cells may provide unique therapeutic options for the treatment of these cardiovascular conditions.
PMCID:10864919
PMID: 38362345
ISSN: 2452-302x
CID: 5635972

Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice

Jiang, Dongyang; Liu, Hao; Zhu, Guofu; Li, Xiankai; Fan, Linlin; Zhao, Faxue; Xu, Chong; Wang, Shumin; Rose, Yara; Rhen, Jordan; Yu, Ze; Yin, Yiheng; Gu, Yuling; Xu, Xiangbin; Fisher, Edward A; Ge, Junbo; Xu, Yawei; Pang, Jinjiang
BACKGROUND:(phosphatase and actin regulator 1) locus strongly correlate with coronary artery disease. However, the biological function of PHACTR1 remains poorly understood. Here, we identified the proatherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1. METHODS: RESULTS:KO on EC activation and atherosclerosis in vivo. CONCLUSIONS:Our results identified endothelial PHACTR1 as a novel PPARγ corepressor to promote atherosclerosis in disturbed flow regions. Endothelial PHACTR1 is a potential therapeutic target for atherosclerosis treatment.
PMID: 37199156
ISSN: 1524-4636
CID: 5508052

Macrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice

Yu, Liming; Xu, Lin; Chu, Haiyan; Peng, Jun; Sacharidou, Anastasia; Hsieh, Hsi-Hsien; Weinstock, Ada; Khan, Sohaib; Ma, Liqian; Durán, José Gabriel Barcia; McDonald, Jeffrey; Nelson, Erik R; Park, Sunghee; McDonnell, Donald P; Moore, Kathryn J; Huang, Lily Jun-Shen; Fisher, Edward A; Mineo, Chieko; Huang, Linzhang; Shaul, Philip W
Hypercholesterolemia and vascular inflammation are key interconnected contributors to the pathogenesis of atherosclerosis. How hypercholesterolemia initiates vascular inflammation is poorly understood. Here we show in male mice that hypercholesterolemia-driven endothelial activation, monocyte recruitment and atherosclerotic lesion formation are promoted by a crosstalk between macrophages and endothelial cells mediated by the cholesterol metabolite 27-hydroxycholesterol (27HC). The pro-atherogenic actions of macrophage-derived 27HC require endothelial estrogen receptor alpha (ERα) and disassociation of the cytoplasmic scaffolding protein septin 11 from ERα, leading to extranuclear ERα- and septin 11-dependent activation of NF-κB. Furthermore, pharmacologic inhibition of cyp27a1, which generates 27HC, affords atheroprotection by reducing endothelial activation and monocyte recruitment. These findings demonstrate cell-to-cell communication by 27HC, and identify a major causal linkage between the hypercholesterolemia and vascular inflammation that partner to promote atherosclerosis. Interventions interrupting this linkage may provide the means to blunt vascular inflammation without impairing host defense to combat the risk of atherosclerotic cardiovascular disease that remains despite lipid-lowering therapies.
PMCID:10368733
PMID: 37491347
ISSN: 2041-1723
CID: 5592122

β-carotene accelerates resolution of atherosclerosis by promoting regulatory T cell expansion in the atherosclerotic lesion

Pinos, Ivan; Coronel, Johana; Albakri, Asma"™A; Blanco, Amparo; McQueen, Patrick; Molina, Donald; Sim, Jaeyoung; Fisher, Edward A.; Amengual, Jaume
β-carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that β-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in Bco1-/- mice implicate vitamin A production in the effects of β-carotene on atherosclerosis resolution. To explore the direct implication of dietary β-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that β-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of β-carotene on atherosclerosis resolution. Our data highlight the potential of β-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.
SCOPUS:85165487128
ISSN: 2050-084x
CID: 5548742

Abstract 441: Relationship Between Diabetes, Glucose Control, And Vascular Health: Findings From The American Heart Association Cardiometabolic Health Strategically Focused Research Network [Meeting Abstract]

Garshick, Michael; Barrett, Tessa A; Jindal, Manila; Newman, Jonathan D; Fadzan, Maja; Bredefeld, Cindy; Levy, Natalie; Akinlonu, Adedoyin; Heguy, Adriana; Drenkova, Schlamp, Florencia; Giannarelli, Chiara; Fisher, Edward A; Goldberg, Ira J; Berger, Jeffrey
ORIGINAL:0017100
ISSN: 1524-4636
CID: 5578852