scholarly journals Peripheral artery disease is associated with severe impairment of vascular function

2013 ◽  
Vol 18 (2) ◽  
pp. 72-78 ◽  
Author(s):  
Soroosh Kiani ◽  
Jonathan G Aasen ◽  
Monika Holbrook ◽  
Abhishek Khemka ◽  
Farhana Sharmeen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Peripheral Artery ◽  
Severe Impairment ◽  
Artery Disease

Abstract 11: Effects of Canakinumab in Patients With Peripheral Artery Disease

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kerry S Russell ◽  
Denise Yates ◽  
Andrea Feller ◽  
Tianke Wang ◽  
Ping Chen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Cardiovascular Events ◽  
Ankle Brachial Index ◽  
Unmet Need ◽  
Walking Distance ◽  
Plaque Progression ◽  
Peripheral Artery ◽  
Plaque Volume ◽  
Artery Disease

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.

scholarly journals Leg heat therapy improves perceived physical function but does not enhance walking capacity or vascular function in patients with peripheral artery disease

2020 ◽  
Vol 129 (6) ◽  
pp. 1279-1289
Author(s):  
Jacob C. Monroe ◽  
Chen Lin ◽  
Susan M. Perkins ◽  
Yan Han ◽  
Brett J. Wong ◽  
...  
Keyword(s):  
Physical Function ◽  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Controlled Study ◽  
Peripheral Artery ◽  
Walking Capacity ◽  
Heat Therapy ◽  
Walking Performance ◽  
Artery Disease ◽  
Potent Vasoconstrictor

This is the first sham-controlled study to investigate the effects of leg heat therapy (HT) on walking performance, vascular function, and quality of life in patients with peripheral artery disease (PAD). Adherence to HT was high, and the treatment was well tolerated. Our findings revealed that HT applied with water-circulating trousers evokes a clinically meaningful increase in perceived physical function and reduces the serum concentration of the potent vasoconstrictor endothelin-1 in patients with PAD.

Acute effects of walking and combined exercise on oxidative stress and vascular function in peripheral artery disease

2016 ◽  
Vol 38 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Aluísio H. R. A. Lima ◽  
Marilia A. Correia ◽  
Antônio H. G. Soares ◽  
Breno Q. Farah ◽  
Cláudia L. M. Forjaz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Acute Effects ◽  
Peripheral Artery ◽  
Combined Exercise ◽  
Artery Disease

scholarly journals Dietary Nitrate Intake Improves Vascular Function And Walking Capacity In Patients With Peripheral Artery Disease

2020 ◽  
Vol 52 (7S) ◽  
pp. 894-895
Author(s):  
TeSean K. Wooden ◽  
Elizabeth J. Pekas ◽  
Ronald J. Headid ◽  
Won-Mok Son ◽  
Song-Young Park
Keyword(s):  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Peripheral Artery ◽  
Dietary Nitrate ◽  
Nitrate Intake ◽  
Walking Capacity ◽  
Artery Disease

scholarly journals Dysregulation of ghrelin in diabetes impairs the vascular reparative response to hindlimb ischemia in a mouse model; clinical relevance to peripheral artery disease

2020 ◽  
Author(s):  
Joshua Neale ◽  
James Pearson ◽  
Kate Thomas ◽  
Hirotsugu Tsuchimouchi ◽  
Hiroshi Hosoda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Micro Rna ◽  
Doppler Imaging ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Circulating Levels

Abstract Background: Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD. Moreover, this study aimed to demonstrate the therapeutic potential of exogenous ghrelin in a diabetic mouse model of PAD. Methods: Standard ELISA analysis was used to quantify and compare circulating levels of ghrelin between i) human diabetic patients with or without PAD (clinic) and ii) db/db diabetic and non-diabetic mice (lab). Db/db mice underwent unilateral hindlimb ischaemia (HLI) for 14 days and treated with or without exogenous ghrelin (150 µg/kg/day.) Subsequently vascular reparation, angiogenesis, hindlimb perfusion, structure and function were assessed using laser Doppler imaging, micro-CT, microangiography, and protein and micro-RNA (miRNA) analysis. We further examined hindlimb perfusion recovery of ghrelin KO mice to determine whether an impaired vascular response to HLI is linked to ghrelin dysregulation in diabetes.Results: Patients with PAD, with or without diabetes, had significantly lower circulating levels of endogenous ghrelin, compared to healthy individuals. Diabetic db/db mice had ghrelin levels that were only 7% of non-diabetic mice. The vascular reparative capacity of diabetic db/db mice in response to HLI was impaired compared to non-diabetic mice and, importantly, comparable to ghrelin KO mice. Daily therapeutic treatment of db/db mice with ghrelin for 14 days post HLI, stimulated angiogenesis, and improved skeletal muscle architecture and cell survival, which was associated with an increase in pro-angiogenic miRNAs-126 and -132.Conclusions: These findings unmask an important role for endogenous ghrelin in vascular repair following limb ischemia, which appears to be downregulated in diabetic patients. Moreover, these results implicate exogenous ghrelin as a potential novel therapy to enhance perfusion in patients with lower limb PAD, especially in diabetics.

scholarly journals Dysregulation of ghrelin in diabetes impairs the vascular reparative response to hindlimb ischemia in a mouse model; clinical relevance to peripheral artery disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joshua P. H. Neale ◽  
James T. Pearson ◽  
Kate N. Thomas ◽  
Hirotsugu Tsuchimochi ◽  
Hiroshi Hosoda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Peripheral Artery Disease ◽  
Vascular Function ◽  
Micro Rna ◽  
Doppler Imaging ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Circulating Levels

Abstract Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD. Moreover, this study aimed to demonstrate the therapeutic potential of exogenous ghrelin in a diabetic mouse model of PAD. Standard ELISA analysis was used to quantify and compare circulating levels of ghrelin between (i) human diabetic patients with or without PAD (clinic) and (ii) db/db diabetic and non-diabetic mice (lab). Db/db mice underwent unilateral hindlimb ischaemia (HLI) for 14 days and treated with or without exogenous ghrelin (150 µg/kg/day.) Subsequently vascular reparation, angiogenesis, hindlimb perfusion, structure and function were assessed using laser Doppler imaging, micro-CT, microangiography, and protein and micro-RNA (miRNA) analysis. We further examined hindlimb perfusion recovery of ghrelin KO mice to determine whether an impaired vascular response to HLI is linked to ghrelin dysregulation in diabetes. Patients with PAD, with or without diabetes, had significantly lower circulating levels of endogenous ghrelin, compared to healthy individuals. Diabetic db/db mice had ghrelin levels that were only 7% of non-diabetic mice. The vascular reparative capacity of diabetic db/db mice in response to HLI was impaired compared to non-diabetic mice and, importantly, comparable to ghrelin KO mice. Daily therapeutic treatment of db/db mice with ghrelin for 14 days post HLI, stimulated angiogenesis, and improved skeletal muscle architecture and cell survival, which was associated with an increase in pro-angiogenic miRNAs-126 and -132. These findings unmask an important role for endogenous ghrelin in vascular repair following limb ischemia, which appears to be downregulated in diabetic patients. Moreover, these results implicate exogenous ghrelin as a potential novel therapy to enhance perfusion in patients with lower limb PAD, especially in diabetics.

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