Abstract 11: The Role of Human Osteopontin Isoforms in Post-Ischemic Neovascularization

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Alicia N Lyle ◽  
Courtney M Caroti ◽  
Grace Sang Hee Lee ◽  
Giji Joseph ◽  
Saghar Harirforoosh ◽  
...  
Keyword(s):  
Mrna Level ◽  
Limb Ischemia ◽  
Volume Density ◽  
Peripheral Artery ◽  
Limb Perfusion ◽  
Isoform Expression ◽  
Artery Disease ◽  
Peripheral Artery Diseases ◽  
And Control

Coronary and peripheral artery diseases lead to ischemia, initiating processes that promote neovascularization to restore blood flow and preserve tissue function. We demonstrated previously that osteopontin (OPN), a matricellular cytokine, is critical to ischemia-induced neovascularization. Unlike rodents, humans express 3 OPN isoforms (a, b, and c); however, the roles of these isoforms in neovascularization and cell migration remain undefined. To assess how human OPN isoforms affect neovascularization, OPN -/- mice underwent hind limb ischemia surgery. At the time of surgery, 1.5x10 6 lentivirus particles expressing human OPNa, OPNb or OPNc were delivered by intramuscular injection. While OPNa improved limb perfusion 30.4%±0.8 in OPN -/- mice, OPNc improved perfusion by 70.9%±6.3 (d14; p<0.001 vs. LVGFP), as measured by laser Doppler perfusion imaging. Importantly, both OPNa and OPNc isoforms significantly rescued neovascularization better than OPNb (n=6, p<0.05). Isoform effects on vascular volume, density, connectivity and diameter were further assessed using Micro-CT angiograms. OPNa and OPNc rescued limb function compared to control and OPNb treated animals (61.1%±8.2; 76.2%±9.7; p<0.05), as assessed by voluntary running wheel use. To verify the differences in neovascularization were due to divergent effects on receptor binding and/or signaling and not variations in isoform expression, we confirmed similar OPN isoform expression levels by ELISA (n=6, p=ns) and immunofluorescence. OPN isoforms a and c both increased macrophage infiltration 2.5 fold, as assessed by mRNA (d7; p<0.05) and histology, leading to increases in vascular smooth muscle cell (VSMC) infiltration (d7; p<0.05). Several pro-arteriogenic factors were also significantly increased at the mRNA level. Finally, we confirmed in vitro that OPNa and OPNc significantly increased VSMC migration compared to OPN b and control (49.8%±3.1; 75.2%±6.3; p<0.05). In conclusion, human OPN isoforms may exhert divergent effects on neovascularization through varried effects on macrophage and VSMC recruitment. Human OPN isoforms may represent potential new therapeutic targets to promote neovascularization and preserve function in patients with peripheral artery disease.

scholarly journals Development of an Exercise Training Protocol to Investigate Arteriogenesis in a Murine Model of Peripheral Artery Disease

2019 ◽  
Vol 20 (16) ◽  
pp. 3956 ◽  
Author(s):  
Ayko Bresler ◽  
Johanna Vogel ◽  
Daniel Niederer ◽  
Daphne Gray ◽  
Thomas Schmitz-Rixen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Suitable Model ◽  
Peripheral Artery ◽  
Running Wheel ◽  
Limb Perfusion ◽  
Collateral Growth ◽  
Artery Disease ◽  
Set Up ◽  
Exercise Induced ◽  
And Control

Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to develop an animal model to stimulate collateral growth in mice through exercise. The training intensity assessment consisted of comparing two different training regimens in C57BL/6 mice, a treadmill implementing forced exercise and a free-to-access voluntary running wheel. The mice in the latter group covered a much greater distance than the former pre- and postoperatively. C57BL/6 mice and hypercholesterolemic ApoE-deficient (ApoE−/−) mice were subjected to FAL and had either access to a running wheel or were kept in motion-restricting cages (control) and hind limb perfusion was measured pre- and postoperatively at various times. Perfusion recovery in C57BL/6 mice was similar between the groups. In contrast, ApoE−/− mice showed significant differences between training and control 7 d postoperatively with a significant increase in pericollateral macrophages while the collateral diameter did not differ between training and control groups 21 d after surgery. ApoE−/− mice with running wheel training is a suitable model to simulate exercise induced collateral growth in PAD. This experimental set-up may provide a model for investigating molecular training effects.

scholarly journals Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association

Circulation ◽  
2019 ◽  
Vol 140 (12) ◽  
Author(s):  
Sanjay Misra ◽  
Mehdi H. Shishehbor ◽  
Edwin A. Takahashi ◽  
Herbert D. Aronow ◽  
Luke P. Brewster ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Critical Limb Ischemia ◽  
Ankle Brachial Index ◽  
Limb Ischemia ◽  
The United States ◽  
Peripheral Artery ◽  
Limb Perfusion ◽  
Scientific Statement ◽  
Artery Disease ◽  
White Patients

There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed.

scholarly journals Angiogenin—A Proposed Biomarker for Cardiovascular Disease—Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease

Angiology ◽  
2021 ◽  
pp. 000331972110043
Author(s):  
Clemens Höbaus ◽  
Gerfried Pesau ◽  
Bernhard Zierfuss ◽  
Renate Koppensteiner ◽  
Gerit-Holger Schernthaner
Keyword(s):  
Peripheral Artery Disease ◽  
Cox Regression ◽  
Ankle Brachial Index ◽  
Limb Ischemia ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Artery ◽  
Cross Sectional ◽  
Term Survival ◽  
Artery Disease

We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men ( P = .001) and were associated with patient waist-to-hip ratio ( P < .001), fasting triglycerides ( P = .011), and inversely with estimated glomerular filtration rate ( P = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.

Multi-Level Lower Extremity Arterial Revascularization Via Retrograde Pedal Access Under Local Anesthesia in a Patient With Severe Cardiopulmonary Comorbidities: A Case Report

2021 ◽  
pp. 153857442110264
Author(s):  
Hee Korleski ◽  
Laura DiChiacchio ◽  
Luiz Araujo ◽  
Michael R. Hall
Keyword(s):  
Case Report ◽  
General Anesthesia ◽  
Peripheral Artery Disease ◽  
Critical Limb Ischemia ◽  
Treatment Modality ◽  
Conventional Treatment ◽  
Limb Ischemia ◽  
Peripheral Artery ◽  
Endovascular Revascularization ◽  
Artery Disease

Background: Chronic limb-threatening ischemia is a severe form of peripheral artery disease that leads to high rates of amputation and mortality if left untreated. Bypass surgery and antegrade endovascular revascularization through femoral artery access from either side are accepted as conventional treatment modalities for critical limb ischemia. The retrograde pedal access revascularization is an alternative treatment modality useful in specific clinical scenarios; however, these indications have not been well described in literature. This case report highlights the use of retrograde pedal access approach as primary treatment modality in a patient with an extensive comorbidities precluding general anesthesia nor supine positioning. Case Presentation: The patient is a 60-year-old female with multiple severe cardiopulmonary comorbidities presenting with dry gangrene of the right great toe. Her comorbidities and inability to tolerate supine positioning precluded her from receiving open surgery, general anesthesia or monitored sedation, or percutaneous femoral access. Rather, the patient underwent ankle block and retrograde endovascular revascularization via dorsalis pedis artery access without post-operative complications. Discussion: The prevalence of comorbidities related to peripheral artery disease is increasing and with it the number of patients who are not optimal candidates for conventional treatment methods for critical limb ischemia. The retrograde pedal access revascularization as initial treatment modality offers these patients an alternative limb salvaging treatment option.

Morphometric Registration of Cytotoxic Changes of Epithelial Cells In Vitro: A Methodological Study

1990 ◽  
Vol 17 (3) ◽  
pp. 174-176
Author(s):  
Lis Andersen ◽  
Dorthe Arenholt-Bindslev
Keyword(s):  
Culture System ◽  
Optimal Allocation ◽  
Volume Density ◽  
Cell Culture System ◽  
Allocation Of Resources ◽  
Methodological Study ◽  
Epithelial Cell Culture ◽  
Coefficients Of Variation ◽  
And Control

Quantification of toxicity-induced cytomorphological effects in an epithelial cell culture system is described. Estimates of volume density and star volume of mitochondria and lysosomes are given. Mean volumes (n = 5) and coefficients of variation of these parameters were equal in experimental (TPA-treatment) and control cultures. An optimal allocation of resources for estimating cytomorphometric parameters would be to increase the number of culture flasks.

Advances in Revascularization for Peripheral Artery Disease: Revascularization in PAD

2021 ◽  
Vol 128 (12) ◽  
pp. 1885-1912
Author(s):  
Joshua A. Beckman ◽  
Peter A. Schneider ◽  
Michael S. Conte
Keyword(s):  
Intermittent Claudication ◽  
Peripheral Artery Disease ◽  
Clinical Presentation ◽  
Rapid Development ◽  
Microvascular Disease ◽  
Limb Ischemia ◽  
Medical Emergency ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Artery Disease

Effective revascularization of the patient with peripheral artery disease is about more than the procedure. The approach to the patient with symptom-limiting intermittent claudication or limb-threatening ischemia begins with understanding the population at risk and variation in clinical presentation. The urgency of revascularization varies significantly by presentation; from patients with intermittent claudication who should undergo structured exercise rehabilitation before revascularization (if needed) to those with acute limb ischemia, a medical emergency, who require revascularization within hours. Recent years have seen the rapid development of new tools including wires, catheters, drug-eluting technology, specialized balloons, and biomimetic stents. Open surgical bypass remains an important option for those with advanced disease. The strategy and techniques employed vary by clinical presentation, lesion location, and lesion severity. There is limited level 1 evidence to guide practice, but factors that determine technical success and anatomic durability are largely understood and incorporated into decision-making. Following revascularization, medical therapy to reduce adverse limb outcomes and a surveillance plan should be put in place. There are many hurdles to overcome to improve the efficacy of lower extremity revascularization, such as restenosis, calcification, microvascular disease, silent embolization, and tools for perfusion assessment. This review highlights the current state of revascularization in peripheral artery disease with an eye toward technologies at the cusp, which may significantly impact current practice.

Abstract MP17: Galectin-3 and Subsequent Risk of Lower-extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Kunihiro Matsushita ◽  
Chao Yang ◽  
Shoshana H Ballew ◽  
John W McEvoy ◽  
Maya Salameh ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Limb Ischemia ◽  
Continuous Variable ◽  
Tissue Loss ◽  
Peripheral Artery ◽  
Cox Models ◽  
Galectin 3 ◽  
Table Model ◽  
Artery Disease

Background: Galectin-3 is involved in the regulation of inflammation and the formation of fibrosis and has been liked to atherosclerosis. However, there are no studies investigating prospective associations of galectin-3 with incidence of lower-extremity peripheral artery disease (PAD). Methods: Among 9,827 ARIC participants without a history of PAD, we investigated whether galectin-3 (measured at visit 4 [1996-98]) was associated with incident clinical PAD through 2013, defined as hospitalizations with PAD diagnosis or leg revascularization. We defined PAD cases with rest pain or tissue loss as critical limb ischemia (CLI). We constructed Cox models with galectin-3 modeled categorically (quartiles) and continuously (log transformed). Results: During a median follow-up of 15.8 years, 287 participants developed PAD (105 incident CLI cases). In demographically adjusted models, galectin-3 demonstrated a dose-response association with incident PAD: hazard ratios (HRs) 2.55 (95% CI 1.80-3.61) and 1.69 (1.18-2.41) for the highest and second highest quartiles, as compared to the lowest quartile (Table; Model 1). Additional adjustment for traditional cardiovascular risk factors attenuated the associations, although the highest quartile remained borderline significant (HR 1.44 [0.99-2.07], p=0.051, Table: Model 2) and galectin-3 as a continuous variable remained significant (1.15 [1.02-1.29]). Similar results were observed for the association of galectin-3 with CLI. Conclusions: Galectin-3 was modestly associated with future risk of clinical PAD events in a community-based cohort, supporting the involvement of inflammation and fibrosis in the development of clinical PAD.

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