Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease

Weiss, Dustin J.; Casale, George P.; Koutakis, Panagiotis; Nella, Aikaterini A.; Swanson, Stanley A.; Zhu, Zhen; Miserlis, Dimitrios; Johanning, Jason M.; Pipinos, Iraklis I.

doi:10.1186/1479-5876-11-230

Cited by 108 publications

(160 citation statements)

References 35 publications

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“…92, 93 Muscle fiber degeneration is associated with evidence of oxidative stress, including carbonyl groups and 4-hydroxy-2-nonenal adducts, protein modifications produced by reactive oxygen species. 94 Mitochondrial function is also important in angiogenesis, consistent with the notion of coupling of vascular and muscular parameters. In hindlimb ischemia models, peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator of mitochondrial biogenesis, promotes vascular regeneration.…”

Section: Vascular Dysfunction In Padmentioning

confidence: 57%

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Hamburg

Creager

2017

Circ J

157

124

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estimates a more than 30% increase in deaths and disability attributable to PAD between 2005 and 2015, which is largely determined by population aging. 3,12 PAD prevalence escalates with advancing age, affecting 1 in 10 adults older than 70 years. In addition to age, smoking and diabetes are the strongest risk factors for PAD across the world. A comprehensive global evaluation of PAD found that its prevalence and risk factors are similar in high-income countries to low-and middle-income countries. 2,13 Lower socioeconomic status is a newly recognized risk factor for PAD. 14 Importantly, there has been a greater increase in PAD prevalence in low-and middle-income countries, rising by 28.7% from 2000 to 2010 as compared with 13.1% in high-income countries. 2, 15 The changing burden of PAD is also greater in women as compared with men.The health implications of PAD derive from both its limb and cardiovascular manifestations. Consistent with the systemic nature of atherosclerosis, polyvascular disease is common in patients with PAD. 16 In the REACH registry, 61% of PAD patients had concomitant coronary artery disease (CAD) and/or cerebrovascular disease. 16 Thus, the presence of PAD portends a high risk for subsequent cardiovascular events. A meta-analysis of over 48,000 participants in population-based cohort studies demonstrated that a low ankle-brachial index (ABI) predicted a 2-fold risk of death, cardiovascular death, and major coronary events at all ranges of the Framingham Risk Score. 4 Further, the elevated risk of cardiovascular events is present in both symptomatic and asymptomatic patients. 17 Patients with atherosclerotic disease in more than 1 vascular territory have particularly poor outcomes. 6 In the over 5,000 Japanese T here is growing recognition of the effect of peripheral artery disease (PAD) on cardiovascular health. 1 Recent studies indicate that, globally, over 200 million adults have PAD, 2,3 which is an expression of systemic atherosclerosis and well-established as heightening the risk for cardiovascular events. 4-6 The limb manifestations of PAD induce considerable suffering. Patients with PAD experience intermittent claudication, characterized as exertional leg pain that limits walking ability, and often times, disability. 7-9 Current medical therapies to reduce the burden of lower extremity symptoms in patients with PAD are limited. Revascularization by endovascular intervention or surgical reconstruction is used to treat lifestyle-limiting claudication if patients do not respond adequately to medical therapy including exercise training. Indeed, lower extremity revascularization with endovascular approaches has undergone a dramatic increase in use. 10 Though endovascular therapy improves blood flow and function, there are significant associated risks, and durability may be limited, especially in infrainguinal disease. Abundant evidence demonstrates the benefits of exercise therapy in claudication, yet the mechanisms underlying the beneficial effects remain incompletely defined. 11 Thus, ...

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Section: Vascular Dysfunction In Padmentioning

confidence: 57%

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Hamburg

Creager

2017

Circ J

157

124

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“…The method has been previously described in detail (Cluff et al 2013;Huang et al 2007;Koutakis et al 2014;Weiss et al 2013). Briefly fluorescence images were captured with a 10× objective of a widefield, epifluorescence microscope (Leica DMRXA2; North Central Instruments, Plymouth, MN) and a B/W CCD camera (Orca ER C4742-95; Hamamatsu Photonics, Bridgewater, NJ), with HCImage software (Hamamatsu, Sewickley, PA).…”

Section: Image Acquisition and Analysismentioning

confidence: 99%

“…Desmin quantification within individual myofibers and myofiber morphometry were based on three-channel imaging (Huang et al 2010;Huang et al 2007;Weiss et al 2013) of each microscopic field. The method has been previously described in detail (Cluff et al 2013;Huang et al 2007;Koutakis et al 2014;Weiss et al 2013).…”

Section: Image Acquisition and Analysismentioning

confidence: 99%

“…Work from several laboratories including our own has demonstrated a myopathy in the affected lower extremities of patients with PAD, which is characterized by mitochondrial dysfunction, increased oxidative damage, myofiber degeneration, muscle fibrosis and decreased muscle force production (Brass and Hiatt 2000;Cluff et al 2013;Hedberg et al 1989;Hedberg et al 1988b; Koutakis et al 2010a;Makitie and Teravainen 1977;Makris et al 2007;Marbini et al 1986;McDermott et al 2004;McDermott et al 2012;Pipinos et al 2007;Pipinos et al 2003;Regensteiner et al 1993;Weiss et al 2013). This myopathy is closely related to leg function, daily activity, quality of life and even mortality of patients with PAD (Anderson et al 2009;Brass 1996;Evans et al 2011;Gardner et al 2013;Garg et al 2011;McDermott et al 2009;McDermott et al 2012; Thompson et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…This myopathy is closely related to leg function, daily activity, quality of life and even mortality of patients with PAD (Anderson et al 2009;Brass 1996;Evans et al 2011;Gardner et al 2013;Garg et al 2011;McDermott et al 2009;McDermott et al 2012; Thompson et al 2014). Furthermore, worsening of the myopathy is associated with progression of PAD from claudication to rest pain and tissue loss (Cluff et al 2013;Weiss et al 2013). Investigations into the pathophysiology of PAD myopathy have focused largely on the myofibers and their contractile elements, with very little attention given to the myofiber cytoskeleton.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal Accumulation of Desmin in Gastrocnemius Myofibers of Patients with Peripheral Artery Disease

Koutakis¹,

Miserlis

Myers

et al. 2015

J Histochem Cytochem.

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SummaryPatients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD. (J Histochem Cytochem 63:256-269, 2015)

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Precise Regulation of Inflammation and Oxidative Stress by ROS‐Responsive Prodrug Coated Balloon for Preventing Vascular Restenosis

Zhao

Jia

et al. 2023

Adv Funct Materials

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Vascular restenosis after balloon dilation is largely caused by the over‐proliferation of smooth muscle cells, which is triggered and exacerbated by local excessive inflammation and oxidative stress. The excessive inflammatory and oxidative stress cause tissue/cell damage, hamper endothelial functions, and worsen intimal hyperplasia and restenosis. A high level of reactive oxygen species (ROS) overproduction is regarded as the main culprit. Therefore, efficiently inhibiting ROS over‐production or weightily depleting them is of great significance. Herein, a “ROS‐responsive/scavenging prodrug” is introduced into balloon coating for the treatment of vascular restenosis. A reversible phenylboronic ester‐bearing caffeic acid (CA) macromolecular prodrug (PBC) is designed for the controlled and on‐demand dual‐drug release triggered by the local high ROS level; the released CA and 4‐hydroxybenzyl alcohol exhibit efficient antioxidant and anti‐inflammatory effects by scavenging ROS, thereby regulating vascular microenvironment and protecting endothelium functions. To accelerate endothelium regeneration, pro‐endothelial microRNA‐126 is further introduced. The ROS‐responsive/scavenging prodrug/miRNA balloon coating efficiently prevents intimal hyperplasia, alleviates local inflammation, and improves endothelium healing in a rat abdominal aorta restenosis model, which may provide applicative perspectives for next‐generation drug‐coated balloons and other cardiovascular diseases treatment.

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Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease

Cited by 108 publications

References 35 publications

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Pathophysiology of Intermittent Claudication in Peripheral Artery Disease

Abnormal Accumulation of Desmin in Gastrocnemius Myofibers of Patients with Peripheral Artery Disease

Precise Regulation of Inflammation and Oxidative Stress by ROS‐Responsive Prodrug Coated Balloon for Preventing Vascular Restenosis

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