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- Vågesjö, Evelina, et al.
(författare)
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Perivascular macrophages regulate blood flow following tissue damage
- 2021
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Ingår i: Circulation Research. - : Lippincott Williams & Wilkins. - 0009-7330 .- 1524-4571. ; 128:11, s. 1694-1707
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Ischemic injuries remain a leading cause of mortality and morbidity worldwide, and restoration of functional blood perfusion is vital to limit tissue damage and support healing.Objective: To reveal a novel role of macrophages in reestablishment of functional tissue perfusion following ischemic injury that can be targeted to improve tissue restoration.Methods and Results: Using intravital microscopy of ischemic hindlimb muscle in mice, and confocal microscopy of human tissues from amputated legs, we found that macrophages accumulated perivascularly in ischemic muscles, where they expressed high levels of iNOS (inducible nitric oxide [NO] synthase). Genetic depletion of iNOS specifically in macrophages (Cx3cr1-CreERT2;Nos2(fl/fl) or LysM-Cre;Nos2(fl/fl)) did not affect vascular architecture but highly compromised blood flow regulation in ischemic but not healthy muscle, which resulted in aggravated ischemic damage. Thus, the ability to upregulate blood flow was shifted from eNOS (endothelial)-dependence in healthy muscles to completely rely on macrophage-derived iNOS during ischemia. Macrophages in ischemic muscles expressed high levels of CXCR4 (C-X-C chemokine receptor type 4) and CCR2 (C-C chemokine receptor type 2), and local overexpression by DNA plasmids encoding the corresponding chemokines CXCL12 (stromal-derived factor 1) or CCL2 (chemokine [C-C motif] ligand 2) increased macrophage numbers, while CXCL12 but not CCL2 induced their perivascular positioning. As a result, CXCL12-overexpression increased the number of perfused blood vessels in the ischemic muscles, improved functional muscle perfusion in a macrophage-iNOS-dependent manner, and ultimately restored limb function.Conclusions: This study establishes a new function for macrophages during tissue repair, as they regulate blood flow through the release of iNOS-produced NO. Further, we demonstrate that macrophages can be therapeutically targeted to improve blood flow regulation and functional recovery of ischemic tissues.
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- Callaghan, Terry, et al.
(författare)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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- Esbjörnsson, M, et al.
(författare)
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Sprint exercise enhances skeletal muscle p70S6k phosphorylation and more so in women than in men.
- 2012
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 205:3, s. 411-22
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Sprint exercise is characterized by repeated sessions of brief intermittent exercise at a high relative workload. However, little is known about the effect on mTOR pathway, an important link in the regulation of muscle protein synthesis. An earlier training study showed a greater increase in muscle fibre cross-sectional area in women than men. Therefore, we tested the hypothesis that the activation of mTOR signalling is more pronounced in women than in men. Healthy men (n=9) and women (n=8) performed three bouts of 30-s sprint exercise with 20-min rest in between.METHODS: Multiple blood samples were collected over time, and muscle biopsy specimens were obtained at rest and 140 min after the last sprint.RESULTS: Serum insulin increased by sprint exercise and more so in women than in men [gender (g) × time (t)]: P=0.04. In skeletal muscle, phosphorylation of Akt increased by 50% (t, P=0.001) and mTOR by 120% (t, P=0.002) independent of gender. The elevation in p70S6k phosphorylation was larger in women (g × t, P=0.03) and averaged 230% (P=0.006) as compared to 60% in men (P=0.04). Phosphorylation rpS6 increased by 660% over time independent of gender (t, P=0.003). Increase in the phosphorylation of p70S6k was directly related to increase in serum insulin (r=0.68, P=0.004).CONCLUSION: It is concluded that repeated 30-s all-out bouts of sprint exercise separated by 20 min of rest increases Akt/mTOR signalling in skeletal muscle. Secondly, signalling downstream of mTOR was stronger in women than in men after sprint exercise indicated by the increased phosphorylation of p70S6k.
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- Hopper, I., et al.
(författare)
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Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study
- 2017
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164. ; 23:9, s. 702-707
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. Methods and Results: Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL . min(-1) . 1.73 m(-2)) on stable medical therapy were enrolled. Mean age was 65 +/- 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 +/- 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 +/- 1228 vs 1428 +/- 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 +/- 5.1 vs 9.9 +/- 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 +/- 9% vs 29 +/- 11%; P = .536), 6-minute walk test (384 +/- 96 vs 391 +/- 97 m; P = .584), or eGFR (52.6 +/- 15.3 vs 52.3 +/- 18.5 mL . min(-1) . 1.73 m(-2); P = .700). Conclusions: RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study.
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