A5102786143- Renin-Angiotensin System Studies
- Sodium Intake and Health
- Meningioma and schwannoma management
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hormonal Regulation and Hypertension
- Apelin-related biomedical research
- Birth, Development, and Health
- Receptor Mechanisms and Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Atherosclerosis and Cardiovascular Diseases
- Vascular Malformations Diagnosis and Treatment
- Electrolyte and hormonal disorders
- Peroxisome Proliferator-Activated Receptors
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Vasculitis and related conditions
- Renal Diseases and Glomerulopathies
- Tryptophan and brain disorders
- Neurofibromatosis and Schwannoma Cases
- Neuropeptides and Animal Physiology
- Brain Metastases and Treatment
- Blood Pressure and Hypertension Studies
- Adenosine and Purinergic Signaling
- Complement system in diseases
Cedars-Sinai Medical Center
2015-2025
Hinge Health
2025
New York University
2023-2024
Neurological Surgery
2024
NYU Langone Health
2024
Union Hospital
2021
Huazhong University of Science and Technology
2021
Bernstein Clinical Research Center
2018-2019
Institute of Biomedical Science
2018
Abstract Aims The metabolic failure of macrophages to adequately process lipid is central the aetiology atherosclerosis. Here, we examine role macrophage angiotensin-converting enzyme (ACE) in a mouse model PCSK9-induced Methods and results Atherosclerosis mice was induced with AAV-PCSK9 high-fat diet. Animals increased ACE (ACE 10/10 mice) have marked reduction atherosclerosis vs. WT mice. Macrophages from both aorta peritoneum express PPARα profoundly altered phenotype lipids characterized...
Granulocytes are key players in cancer metastasis. While tumor-induced de novo expansion of immunosuppressive myeloid-derived suppressor cells (MDSCs) is well-described, the fate and contribution terminally differentiated mature neutrophils to metastatic process remain poorly understood. Here, we show that experimental models, CXCR4hiCD62Llo aged accumulate via disruption neutrophil circadian homeostasis direct stimulation aging mediated by angiotensin II. Compared CXCR4loCD62Lhi naive...
Chronic renal inflammation has been widely recognized as a major promoter of several forms high blood pressure including salt-sensitive hypertension. In diabetes, IL (interleukin)-6 induces salt sensitivity through dysregulation the epithelial sodium channel. However, origin this inflammatory process and molecular events that culminates with an abnormal regulation channel in diabetes are largely unknown.Both vitro vivo approaches were used to investigate cellular contributors associated...
Hypertension promotes ATP release from erythrocytes, leading to a P2X7-dependent increase in T cell–mediated immune responses.
Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these often at increased risk infection. To evaluate the impact ACEIs on immune responses infection, we compared effect an ACEI versus angiotensin receptor blocker (ARB) neutrophil antibacterial activity. exposure reduced ability murine neutrophils kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa,...
Macrophages mediate key antimicrobial responses against intracellular bacterial pathogens, such as Salmonella enterica . Yet, they can also act a permissive niche for these pathogens to persist in infected tissues within granulomas, which are immunological structures composed of macrophages and other immune cells. We apply single-cell transcriptomics investigate macrophage functional diversity during persistent S. serovar Typhimurium ( S Tm) infection mice. identify determinants...
Angiotensin-converting enzyme (ACE) affects blood pressure. In addition, ACE overexpression in myeloid cells increases their immune function. Using MS and chemical analysis, we identified marked changes of intermediate metabolites ACE-overexpressing macrophages neutrophils, with increased cellular ATP (1.7-3.0-fold) Krebs cycle intermediates, including citrate, isocitrate, succinate, malate (1.4-3.9-fold). Increased is due to C-domain catalytic activity; it reversed by an inhibitor but not...
Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes injury uncertain. Here, two mouse models with different patterns expression were studied determine the specific contribution tubular vs. glomerular early nephropathy: it-ACE mice, which make endothelial but lack by epithelium, and 3/9 only express epithelial cells. The absence...
Angiotensin-converting enzyme (ACE) can hydrolyze many peptides and plays a central role in controlling blood pressure. Moreover, ACE overexpression monocytes macrophages increases resistance of mice to tumor growth. is composed two independent catalytic domains. Here, investigate the specific each domain resistance, we overexpressed either WT (Tg-ACE mice) or lacking N- C-domain activity (Tg-NKO Tg-CKO myeloid cells mice. Tg-ACE Tg-NKO exhibited strongly suppressed growth B16-F10 melanoma...
Angiotensin-converting enzyme (ACE) affects blood pressure. In addition, ACE overexpression in myeloid cells increases their immune function. Using MS and chemical analysis, we identified marked changes of intermediate metabolites ACE-overexpressing macrophages neutrophils, with increased cellular ATP (1.7–3.0-fold) Krebs cycle intermediates, including citrate, isocitrate, succinate, malate (1.4–3.9-fold). Increased is due to C-domain catalytic activity; it reversed by an inhibitor but not...
Significance Statement Men with diabetes have higher incidence of renal disease and hypertension than premenopausal women diabetes. A mouse model investigated the mechanisms that predispose to salt-sensitive during Male, 34-week-old, diabetic mice display when exposed a high-salt diet, whereas females remain normotensive. Hypertension in males was associated greater inflammation no downregulation epithelial sodium channel (ENaC) compared females. Blocking prevented development salt...
Background Recent evidence emphasizes the critical role of inflammation in development diabetic nephropathy. Angiotensin-converting enzyme (ACE) plays an active regulating renal inflammatory response associated with diabetes. Studies have also shown that ACE has roles and immune are independent angiotensin II. ACE’s two catalytically domains, N- C-domains, can process a variety substrates other than I. Methods To examine relative contributions each domain to sodium retentive state,...
Testis angiotensin-converting enzyme (tACE) plays a critical role in male fertility, but the mechanism is unknown. By using ACE C-domain KO (CKO) mice which lack tACE activity, we found that ATP CKO sperm was 9.4-fold lower than WT sperm. Similarly, an inhibitor (ACEi) reduced production mouse by 72%. Metabolic profiling showed inactivation severely affects oxidative metabolism with decreases several Krebs cycle intermediates including citric acid, cis-aconitic NAD, α-ketoglutaric succinate,...
The pathogenesis of atherosclerosis is defined by impaired lipid handling macrophages which increases intracellular accumulation. This dysregulation triggers the accumulation apoptotic cells and chronic inflammation contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. due metabolism...
ABSTRACT Genome-wide association studies (GWAS) have identified many gene polymorphisms associated with an increased risk of developing Late Onset Alzheimer’s Disease (LOAD). Many these LOAD risk-associated alleles alter disease pathogenesis by influencing microglia innate immune responses and lipid metabolism. Angiotensin Converting Enzyme (ACE), a GWAS best known for its role in regulating systemic blood pressure, also enhances immunity processing peripheral myeloid cells, but ACE...