Myocutaneous revascularization following graded ischemia in lean and obese mice
Ross M Clark,1 Brittany Coffman,2 Paul G McGuire,3 Thomas R Howdieshell1,3 1Department of Surgery, 2Department of Pathology, 3Department of Cell Biology and Vascular Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA Background: Murine models of diabetes and obesity ha...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016-09-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Subjects: | |
| Online Access: | https://www.dovepress.com/myocutaneous-revascularization-following-graded-ischemia-in-lean-and-o-peer-reviewed-article-DMSO |
| _version_ | 1811174122779049984 |
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| author | Clark RM Coffman B McGuire PG Howdieshell TR |
| author_facet | Clark RM Coffman B McGuire PG Howdieshell TR |
| author_sort | Clark RM |
| collection | DOAJ |
| description | Ross M Clark,1 Brittany Coffman,2 Paul G McGuire,3 Thomas R Howdieshell1,3 1Department of Surgery, 2Department of Pathology, 3Department of Cell Biology and Vascular Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA Background: Murine models of diabetes and obesity have provided insight into the pathogenesis of impaired epithelialization of excisional skin wounds. However, knowledge of postischemic myocutaneous revascularization in these models is limited. Materials and methods: A myocutaneous flap was created on the dorsum of wild type (C57BL/6), genetically obese and diabetic (ob/ob, db/db), complementary heterozygous (ob+/ob− , db+/db−), and diet-induced obese (DIO) mice (n=48 total; five operative mice per strain and three unoperated mice per strain as controls). Flap perfusion was documented by laser speckle contrast imaging. Local gene expression in control and postoperative flap tissue specimens was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Image analysis of immunochemically stained histologic sections confirmed microvascular density and macrophage presence. Results: Day 10 planimetric analysis revealed mean flap surface area necrosis values of 10.8%, 12.9%, 9.9%, 0.4%, 1.4%, and 23.0% for wild type, db+/db−, ob+/ob−, db/db, ob/ob, and DIO flaps, respectively. Over 10 days, laser speckle imaging documented increased perfusion at all time points with revascularization to supranormal perfusion in db/db and ob/ob flaps. In contrast, wild type, heterozygous, and DIO flaps displayed expected graded ischemia with failure of perfusion to return to baseline values. RT-PCR demonstrated statistically significant differences in angiogenic gene expression between lean and obese mice at baseline (unoperated) and at day 10. Conclusion: Unexpected increased baseline skin perfusion and augmented myocutaneous revascularization accompanied by a control proangiogenic transcriptional signature in genetically obese mice compared to DIO and lean mice are reported. In future research, laser speckle imaging has been planned to be utilized in order to correlate spatiotemporal wound reperfusion with changes in cell recruitment and gene expression to better understand the differences in wound microvascular biology in lean and obese states. Keywords: diabetes, obesity, laser speckle contrast imaging, reperfusion |
| first_indexed | 2024-04-10T17:58:05Z |
| format | Article |
| id | doaj.art-2db8dbab364c4ed3999dcac589900f89 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T17:58:05Z |
| publishDate | 2016-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-2db8dbab364c4ed3999dcac589900f892023-02-02T16:52:22ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072016-09-01Volume 932533629214Myocutaneous revascularization following graded ischemia in lean and obese miceClark RMCoffman BMcGuire PGHowdieshell TRRoss M Clark,1 Brittany Coffman,2 Paul G McGuire,3 Thomas R Howdieshell1,3 1Department of Surgery, 2Department of Pathology, 3Department of Cell Biology and Vascular Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA Background: Murine models of diabetes and obesity have provided insight into the pathogenesis of impaired epithelialization of excisional skin wounds. However, knowledge of postischemic myocutaneous revascularization in these models is limited. Materials and methods: A myocutaneous flap was created on the dorsum of wild type (C57BL/6), genetically obese and diabetic (ob/ob, db/db), complementary heterozygous (ob+/ob− , db+/db−), and diet-induced obese (DIO) mice (n=48 total; five operative mice per strain and three unoperated mice per strain as controls). Flap perfusion was documented by laser speckle contrast imaging. Local gene expression in control and postoperative flap tissue specimens was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Image analysis of immunochemically stained histologic sections confirmed microvascular density and macrophage presence. Results: Day 10 planimetric analysis revealed mean flap surface area necrosis values of 10.8%, 12.9%, 9.9%, 0.4%, 1.4%, and 23.0% for wild type, db+/db−, ob+/ob−, db/db, ob/ob, and DIO flaps, respectively. Over 10 days, laser speckle imaging documented increased perfusion at all time points with revascularization to supranormal perfusion in db/db and ob/ob flaps. In contrast, wild type, heterozygous, and DIO flaps displayed expected graded ischemia with failure of perfusion to return to baseline values. RT-PCR demonstrated statistically significant differences in angiogenic gene expression between lean and obese mice at baseline (unoperated) and at day 10. Conclusion: Unexpected increased baseline skin perfusion and augmented myocutaneous revascularization accompanied by a control proangiogenic transcriptional signature in genetically obese mice compared to DIO and lean mice are reported. In future research, laser speckle imaging has been planned to be utilized in order to correlate spatiotemporal wound reperfusion with changes in cell recruitment and gene expression to better understand the differences in wound microvascular biology in lean and obese states. Keywords: diabetes, obesity, laser speckle contrast imaging, reperfusionhttps://www.dovepress.com/myocutaneous-revascularization-following-graded-ischemia-in-lean-and-o-peer-reviewed-article-DMSOdiabetesobesitylaser speckle contrast imagingrevascularization |
| spellingShingle | Clark RM Coffman B McGuire PG Howdieshell TR Myocutaneous revascularization following graded ischemia in lean and obese mice Diabetes, Metabolic Syndrome and Obesity diabetes obesity laser speckle contrast imaging revascularization |
| title | Myocutaneous revascularization following graded ischemia in lean and obese mice |
| title_full | Myocutaneous revascularization following graded ischemia in lean and obese mice |
| title_fullStr | Myocutaneous revascularization following graded ischemia in lean and obese mice |
| title_full_unstemmed | Myocutaneous revascularization following graded ischemia in lean and obese mice |
| title_short | Myocutaneous revascularization following graded ischemia in lean and obese mice |
| title_sort | myocutaneous revascularization following graded ischemia in lean and obese mice |
| topic | diabetes obesity laser speckle contrast imaging revascularization |
| url | https://www.dovepress.com/myocutaneous-revascularization-following-graded-ischemia-in-lean-and-o-peer-reviewed-article-DMSO |
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