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Limb functional recovery is impaired in fibroblast growth factor-2 (FGF2) deficient mice despite chronic ischaemia-induced vascular growth.

ABSTRACT: FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

SUBMITTER: Adeyemo A

PROVIDER: S-EPMC8601595 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Despite normal arteriogenic and angiogenic responses, hind limb perfusion recovery and necrotic and fibroadipose tissue clearance are impaired in matrix metalloproteinase 9-deficient mice.

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Project description: Not available

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Nitropravastatin stimulates reparative neovascularisation and improves recovery from limb Ischaemia in type-1 diabetic mice.

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Initiation of Conceptus Elongation Coincides with an Endometrium Basic Fibroblast Growth Factor (FGF2) Protein Increase in Heifers.

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| S-EPMC3745640 | biostudies-literature

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Project description:ObjectiveCandida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking.DesignWe investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4 cell counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4 cell counts higher than 500 cells/?l, CD4 cell nadirs higher than 350 cells/?l and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group) and 20 healthy individuals.MethodsWe investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and enzyme-linked immunosorbent spot.ResultsWe found that patients with Candida esophagitis had nearly abolished CD4 cell proliferation in response to Candida albicans, significantly increased percentages of dysfunctional CD4 cells, significantly decreased cytotoxic natural killer cell counts and peripheral innate lymphoid cell counts and significantly reduced IFN-? and IL-17 production compared with the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery.ConclusionOur data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects.

| S-EPMC4949004 | biostudies-literature

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