Browsing by Subject "Vascular"

Now showing 1 - 5 of 5
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    Contemporary Management of Axillo-subclavian Arterial Injuries Using Data from the AAST PROOVIT Registry
    (Division of Cardiothoracic and Vascular Surgery and General Surgery, Örebro University Hospital, Sweden, 2021) Guntur, Grahya; DuBose, Joseph J.; Bee, Tiffany K.; Fabian, Timothy; Morrison, Jonathan; Skarupa, David J.; Inaba, Kenji; Kundi, Rishi; Scalea, Thomas; Feliciano, David V.; AAST PROOVIT Study Group; Surgery, School of Medicine
    Background: Endovascular repair has emerged as a viable repair option for axillo-subclavian arterial injuries in select patients; however, further study of contemporary outcomes is warranted. Methods: The American Association for the Surgery of Trauma (AAST) PROspective Observational Vascular Injury Treatment (PROOVIT) registry was used to identify patients with axillo-subclavian arterial injuries from 2013 to 2019. Demographics and outcomes were compared between patients undergoing endovascular repair versus open repair. Results: 167 patients were identified, with intervention required in 107 (64.1%). Among these, 24 patients underwent open damage control surgery (primary amputation = 3, ligation = 17, temporary vascular shunt = 4). The remaining 83 patients (91.6% male; mean age 26.0 ± 16) underwent either endovascular repair (36, 43.4%) or open repair (47, 56.6%). Patients managed with definitive endovascular or open repair had similar demographics and presentation, with the only exception being that endovascular repair was more commonly employed for traumatic pseudoaneurysms (p = 0.004). Endovascular repair was associated with lower 24-hour transfusion requirements (p = 0.012), but otherwise the two groups were similar with regards to in-hospital outcomes. Conclusion: Endovascular repair is now employed in >40% of axillo-subclavian arterial injuries undergoing repair at initial operation and is associated with lower 24-hour transfusion requirements, but otherwise outcomes are comparable to open repair.
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    Generation of mice carrying a knockout-first and conditional-ready allele of transforming growth factor beta2 gene
    (Wiley, 2014-09) Ahmed, A. S. Ishtiaq; Bose, Gracelyn C.; Huang, Li; Azhar, Mohamad; Department of Pediatrics, Indiana University School of Medicine
    Transforming growth factor beta2 (TGFβ2) is a multifunctional protein which is expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal, ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various forms of cancer. TGFβ2 is involved in cell growth, apoptosis, cell migration, cell differentiation, cell-matrix remodeling, epithelial-mesenchymal transition, and wound healing in a highly context-dependent and tissue-specific manner. Tgfb2(-/-) mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring Tgfb2(βgeo) (knockout-first lacZ-tagged insertion) gene-trap allele and Tgfb2(flox) conditional allele. Tgfb2(βgeo/βgeo) or Tgfb2(βgeo/-) mice died at perinatal stage from the same congenital heart defects as Tgfb2(-/-) mice. β-galactosidase staining successfully detected Tgfb2 expression in the heterozygous Tgfb2(βgeo) fetal tissue sections. Tgfb2(flox) mice were produced by crossing the Tgfb2(+/βgeo) mice with the FLPeR mice. Tgfb2(flox/-) mice were viable. Tgfb2 conditional knockout (Tgfb2(cko/-) ) fetuses were generated by crossing of Tgfb2(flox/-) mice with Tgfb2(+/-) ; EIIaCre mice. Systemic Tgfb2(cko/-) embryos developed cardiac defects which resembled the Tgfb2(βgeo/βgeo) , Tgfb2(βgeo/-) , and Tgfb2(-/-) fetuses. In conclusion, Tgfb2(βgeo) and Tgfb2(flox) mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGFβ2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis
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    Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury
    (American Society of Nephrology, 2017-06) McCurley, Amy; Alimperti, Stella; Campos-Bilderback, Silvia B.; Sandoval, Ruben M.; Calvino, Jenna E.; Reynolds, Taylor L.; Quigley, Catherine; Mugford, Joshua W.; Polacheck, William J.; Gomez, Ivan G.; Dovey, Jennifer; Marsh, Graham; Huang, Angela; Qian, Fang; Weinreb, Paul H.; Dolinski, Brian M.; Moore, Shaun; Duffield, Jeremy S.; Chen, Christopher S.; Molitoris, Bruce A.; Violette, Shelia M.; Crackower, Michael A.; Medicine, School of Medicine
    Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI.
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    Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells
    (Frontiers Media, 2022-03-14) Jiang, Yizhi; Ji, Julie Y.; Biomedical Engineering, Purdue School of Engineering and Technology
    Progerin as a mutated isoform of lamin A protein was first known to induce premature atherosclerosis progression in patients with Hutchinson-Gilford progeria syndrome (HGPS), and its role in provoking an inflammatory response in vascular cells and accelerating cell senescence has been investigated recently. However, how progerin triggers endothelial dysfunction that often occurs at the early stage of atherosclerosis in a mechanical environment has not been studied intensively. Here, we generated a stable endothelial cell line that expressed progerin and examined its effects on endothelial wound repair under laminar flow. We found decreased wound healing rate in progerin-expressing ECs under higher shear stress compared with those under low shear. Furthermore, the decreased wound recovery could be due to reduced number of cells at late mitosis, suggesting potential interference by progerin with endothelial proliferation. These findings provided insights into how progerin affects endothelial mechanotransduction and may contribute to the disruption of endothelial integrity in HGPS vasculature, as we continue to examine the mechanistic effect of progerin in shear-induced endothelial functions.
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    Targeting Early Vascular Dysfunction Following Spinal Cord Injury
    (2019-10) Chen, Chen; Cummins, Theodore R.; Jin, Xiaoming; Jones, Kathryn J.; Yoder, Karmen; Xu, Xiao-ming
    The vascular network highly coordinates with the central nervous system (CNS) on exchanging oxygen, nutrients and information transfer. The resemblance of the two systems at anatomical, cellular, and molecular levels also demonstrates their interdependence. The spinal cord is an integrated part of the CNS. Traumatic spinal cord injury (SCI) causes rapid systemic vascular responses and local neural tissue damage at the initial phase. The early disruption of the spinal vasculature breaks the supply-and-demand balance and facilitates the deterioration of the spinal cord tissue and functional deficits. Therefore, it is important to dissect the mechanism underlying vascular injury-mediated histological and functional consequences in order to develop potential therapeutic strategies. To visualize dynamic vascular changes after an acute SCI, a novel duo-color in vivo imaging technique was successfully developed in adult rats at the cervical level. This technique overcomes previous technical hurdles allowing real-time observation of vascular changes in live animals. Correlated with histological measures, in vivo vascular outcomes revealed a temporospatial relationship with neuronal and axonal loss, myelin disruption, inflammation, and glial responses. For the first time, we defined a “transitional zone” where significant blood vessel dilation and vascular leakage were observed simultaneously with vascular changes occurred at the injury epicenter acutely after SCI. These vascular changes at the transitional zone happened before any other cellular damage after SCI, suggesting a time window to prevent further neuronal damage in this region. Targeting the observed vascular leakage can work as a proof of concept that early vascular dysfunction contributes to the secondary neural tissue damage. Indeed, intravenous delivery of ferulic acid conjugated with glycol chitosan (FA-GC) to the injured sites immediate after SCI resulted in reduced vascular leakage, ventral horn neuronal loss, and partial recovery of forelimb function following a clinically-relevant contusive SCI at the 7th cervical spinal cord level. In conclusion, this work elucidated a novel role and mechanism of early vascular damage in the “transitional zone” prior to the secondary damage of neural tissue in this region and provided a novel treatment strategy for early neuroprotection and functional recovery.