Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease

Ouma, Geoffrey; Jonas, Rebecca; Usman, Muhammad; Mohler, Emile R.

doi:10.1177/1358863x12438270

Cited by 55 publications

(51 citation statements)

References 142 publications

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“…This apparent paradox emphasizes the uncertain relationship among hypoxia, HIF stabilization, and exercise performance, suggesting that therapeutics to improve muscle performance and angiogenesis in PAD should evolve to counter the lack of efficacy in the majority of human trials utilizing molecular, genetic, and cellular modalities. 23 Administration of repeat-dose GSK1278863 15 mg was associated with a decrease from baseline lipid levels. These effects were unexpected and further investigation is warranted.…”

Section: Discussionmentioning

confidence: 99%

“…[23][24][25] Impairment in muscle function and exercise performance in PAD cannot be entirely ascribed to limitation in blood flow. 26 Changes in mitochondrial respiration, microcirculatory function and structure, skeletal muscle organization, nerve-muscle interface, and muscle metabolic function also significantly contribute to the disease pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

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Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease

et al. 2014

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Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). This multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD. The study assessed two active treatment paradigms: single dosing and subchronic daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively). Neither regimen improved exercise performance compared with placebo (change from baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single dose (-46, -44), p=0.96; repeat dose (9, 8), p=0.99; change in number of contractions to onset of claudication (goniometry): single dose (4, -1), p=0.053; repeat dose (-2, 1), p=0.08). A calfmuscle biopsy substudy showed no increases in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863 than placebo experienced adverse events, particularly following the 300 mg single dose. Thus, assessing the safety of GSK1278863 in this setting would require a larger population exposed to the agent for a longer duration. These data do not support a benefit of GSK1278863 in PAD using the regimens tested. ClinicalTrials.gov Identifier: NCT01673555

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease

et al. 2014

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“…9,11 To increase collateral blood vessel development, capillary number, and blood flow, many clinical studies have used the administration of growth factors (mostly basic fibroblast growth factor or vascular endothelial growth factor, either as protein or gene therapy) or stem and progenitor cells. 3,4,8,13,14 In addition, supervised exercise rehabilitation programs have been shown to improve symptoms of claudication, and meta-analyses have found an increase in the average distance walked to the onset of claudication. 15,16 Usual yet imprecise measures of therapeutic effects in clinical studies are absolute walking distance, ulcer healing/decrease of ulcer size or amputation rates, rest pain, and various questionnaires that assess walking impairment or quality of life.…”

Section: Discussionmentioning

confidence: 99%

“…However, in approximately one fourth of these patients, endovascular or surgical therapy fails or is not applicable, which makes alternative approaches necessary. 3,4 Thus, promotion of arteriogenesis, which refers to positive remodeling of preformed collateral arterioles, that is, collateral growth, should be induced in these patients. [4][5][6] …”

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confidence: 99%

Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography

et al. 2013

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Background-Despite the fact that numerous studies have pursued the strategy of improving collateral function in patients with peripheral artery disease, there is currently no method available to quantify collateral arterial function of the lower limb. Methods and Results-Pressure-derived collateral flow index (CFIp, calculated as (occlusive pressure−central venous pressure)/(aortic pressure−central venous pressure); pressure values in mm Hg) of the left superficial femoral artery was obtained in patients undergoing elective coronary angiography using a combined pressure/Doppler wire (n=30). Distal occlusive pressure and toe oxygen saturation (Sao 2 ) were measured for 5 minutes under resting conditions, followed by an exercise protocol (repetitive plantar-flexion movements in supine position; n=28). In all patients, balloon occlusion of the superficial femoral artery over 5 minutes was painless under resting conditions. CFIp increased during the first 3 minutes from 0.451±0.168 to 0.551±0.172 (P=0.0003), whereas Sao 2 decreased from 98±2% to 93±7% (P=0.004). Maximal changes of Sao 2 were inversely related to maximal CFIp (r 2 =0.33, P=0.003). During exercise, CFIp declined within 1 minute from 0.560±0.178 to 0.393±0.168 (P<0.0001) and reached its minimum after 2 minutes of exercise (0.347±0.176), whereas Sao 2 declined to a minimum of 86±6% (P=0.002). Twenty-five patients (89%) experienced pain or cramps/tired muscles, whereas 3 (11%) remained symptom-free for an occlusion time of 10 minutes. CFIp values were positively related to the pain-free time span (r 2 =0.50, P=0.002). Conclusions-Quantitatively assessed collateral arterial function at rest determined in the nonstenotic superficial femoral artery is sufficient to prevent ischemic symptoms during a total occlusion of 5 minutes. During exercise, there is a decline in CFIp that indicates a supply-demand mismatch via collaterals or, alternatively, a steal phenomenon. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01742455.(Circulation. 2013;128:737-744.)

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“…Therapeutic genes can be delivered to the nucleus of cells to repair or substitute defective genes andproduce therapeutic proteins (Ouma, Jonas et al 2012). Suicide genes can be delivered to the nucleus of cancer cells where the gene encodes a protein product that causes cellular apoptosis (Mitry, Sarraf et al 2000;Fillat, Carrio et al 2003).…”

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confidence: 99%

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Nigatu

Vupputuri

Flynn

et al. 2013

Journal of Pharmaceutical Sciences

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Linear low‐density polyethylene (LLDPE), based on butene‐1 or hexene‐1, was irradiated with γ‐rays under vacuum or in the presence of air. The study focused on the influence of the dose rate and the γ‐dose on the thermal properties of LLDPE. Differential scanning calorimetry, thermogravimetric analysis (TGA), and TGA/FTIR techniques were used to address the thermal behavior as a result of γ‐irradiation. During this irradiation, competition between crosslinking and scission reactions, subsequent to oxidation reactions, occurred in the polymeric material, which strongly depends on the experimental conditions. A decrease of the crystallinity for γ‐irradiated samples was observed in particular for samples irradiated under vacuum. This observation may be explained by increased hindrance of segment mobility due to crosslinking reactions that prevent crystal growth. TGA investigations revealed an enhancement of the thermal stability for samples irradiated under vacuum but not for those irradiated in air. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2790–2795, 2006

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Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease

Cited by 55 publications

References 142 publications

Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease

Short-term treatment with a novel HIF-prolyl hydroxylase inhibitor (GSK1278863) failed to improve measures of performance in subjects with claudication-limited peripheral artery disease

Direct Quantitative Assessment of the Peripheral Artery Collateral Circulation in Patients Undergoing Angiography

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

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