Dataset Information

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

ABSTRACT: Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects with severe obesity, suggesting the restoration of a microenvironment to support vessel homeostasis. These data suggest that bariatric surgery may reverse deleterious events that predispose patients with morbid obesity to cardiovascular risk.

SUBMITTER: Hess DA

PROVIDER: S-EPMC7659601 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

Hess David A DA Trac Justin Z JZ Glazer Stephen A SA Terenzi Daniella C DC Quan Adrian A Teoh Hwee H Al-Omran Mohammed M Bhatt Deepak L DL Mazer C David CD Rotstein Ori D OD Verma Subodh S

Cell reports. Medicine 20200519 2

Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerativ ...[more]

PMID: 33205058

Similar Datasets

Project description:BACKGROUND:Activation of transforming growth factor-?-activated kinase 1 (TAK1) occurs after stroke and leads to an exacerbation of brain injury. TAK1 is involved in innate and adaptive immune responses, but it has divergent inflammatory effects that are dependent on the cell type in which it is activated. There is a robust infiltration of myeloid cells after stroke; however, the contribution of myeloid TAK1 to cerebral ischemia is currently unknown. We hypothesized that myeloid-specific deletion of TAK1 would protect against ischemic brain injury. METHODS:Myeloid TAK1?M and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAo). Brain-infiltrating and splenic immune cells were evaluated at 3 days after stroke. Assessment of infarct size and behavioral deficits were performed on days 3 and 7 post-stroke. RESULTS:Infarcts were significantly smaller in TAK1?M mice (p?<?0.01), and behavioral deficits were less severe despite equivalent reduction in cerebral blood flow. Flow cytometry demonstrated an increase in the frequency of splenic monocytes and neutrophils (p?<?0.05) and a decrease in splenic CD3+ T (p?<?0.01) and CD19+ B (p?=?0.06) cells in TAK1?M mice compared to WT at baseline. Three days after stroke, a significant increase in the number of brain-infiltrating immune cell was observed in both TAK1?M (p?<?0.05) and WT (p?<?0.001) mice compared to their respective shams. However, there was a significant decrease in the infiltrating CD45hi immune cell counts (p?<?0.05), with a pronounced reduction in infiltrating monocytes (p?<?0.001) in TAK1?M after stroke compared to WT stroke mice. Additionally, a significant reduction in CD49d+ monocytes was seen in the brains of TAK1?M stroke mice compared to wild-type mice. Importantly, TAK1?M MCAo mice had smaller infarcts and improved behavioral outcomes at day 7 post-stroke. CONCLUSION:Our results showed that deletion of myeloid TAK1 resulted in smaller infarcts and improved functional outcomes at the peak of inflammation (day 3) and a reduction in brain-infiltrating immune cells that were primarily monocytes. Myeloid TAK1 deletion was also protective at 7 days post MCAo, reflecting a detrimental role of myeloid TAK1 in the progression of ischemic injury.

Project description:Besides being a key effector arm of innate immunity, a plethora of non-canonical functions of complement has recently been emerging. Factor H (FH), the main regulator of the alternative pathway of complement activation, has been reported to bind to various immune cells and regulate their functions, beyond its role in modulating complement activation. In this study we investigated the effect of FH, its alternative splice product FH-like protein 1 (FHL-1), the FH-related (FHR) proteins FHR-1 and FHR-5, and the recently developed artificial complement inhibitor mini-FH, on two key innate immune cells, monocytes and neutrophilic granulocytes. We found that, similar to FH, the other factor H family proteins FHL-1, FHR-1 and FHR-5, as well as the recombinant mini-FH, are able to bind to both monocytes and neutrophils. As a functional outcome, immobilized FH and FHR-1 inhibited PMA-induced NET formation, but increased the adherence and IL-8 production of neutrophils. FHL-1 increased only the adherence of the cells, while FHR-5 was ineffective in altering these functions. The adherence of monocytes was increased on FH, recombinant mini-FH and FHL-1 covered surfaces and, except for FHL-1, the same molecules also enhanced secretion of the inflammatory cytokines IL-1β and TNFα. When monocytes were stimulated with LPS in the presence of immobilized FH family proteins, FH, FHL-1 and mini-FH enhanced whereas FHR-1 and FHR-5 decreased the secretion of TNFα; FHL-1 and mini-FH also enhanced IL-10 release compared to the effect of LPS alone. Our results reveal heterogeneous effects of FH and FH family members on monocytes and neutrophils, altering key features involved in pathogen killing, and also demonstrate that FH-based complement inhibitors, such as mini-FH, may have effects beyond their function of inhibiting complement activation. Thus, our data provide new insight into the non-canonical functions of FH, FHL-1, FHR-1 and FHR-5 that might be exploited during protection against infections and in vaccine development.

Dataset Information

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

Publications

Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets