The Role of Mitochondrial Function in Peripheral Arterial Disease: Insights from Translational Studies

Abstract

Recent evidence demonstrates an involvement of impaired mitochondrial function in peripheral arterial disease (PAD) development. Specific impairments have been assessed by different methodological in-vivo (near-infrared spectroscopy, 31P magnetic resonance spectroscopy), as well as in-vitro approaches (Western blotting of mitochondrial proteins and enzymes, assays of mitochondrial function and content). While effects differ with regard to disease severity, chronic malperfusion impacts subcellular energy homeostasis, and repeating cycles of ischemia and reperfusion contribute to PAD disease progression by increasing mitochondrial reactive oxygen species production and impairing mitochondrial function. With the leading clinical symptom of decreased walking capacity due to intermittent claudication, PAD patients suffer from a subsequent reduction of quality of life. Different treatment modalities, such as physical activity and revascularization procedures, can aid mitochondrial recovery. While the relevance of these modalities for mitochondrial functional recovery is still a matter of debate, recent research indicates the importance of revascularization procedures, with increased physical activity levels being a subordinate contributor, at least during mild stages of PAD. With an additional focus on the role of revascularization procedures on mitochondria and the identification of suitable mitochondrial markers in PAD, this review aims to critically evaluate the relevance of mitochondrial function in PAD development and progression.

Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration

“…While exercise can have a direct effect on multiple cell types in the skeletal muscle, major impacts of training are on mitochondrial function, as reviewed elsewhere, 21 as well as through molecular activation of contracting skeletal muscle, imparting both local myocellular effects, and paracrine effects on activating non-muscle cell types such as endothelial cells to promote vascular regeneration. Key myocellular signaling pathways that may drive vascular regeneration by exercise in paracrine fashion are discussed below, followed by a brief description of other cell types through which exercise may mediate limb vascularization.…”

The predictive value of infrared thermal imaging (IRT) for peripheral artery disease: A systematic review

“…The sensitivity changes in skin temperature related to specific disorders have been quantified using thermal imaging. [7,8] The benefits of infrared thermography include the fact that it is not an invasive tool, quick, dependable, contactless, capable of creating several recordings immediately, and secure for both patients and medical professionals. Recent applications include the diagnosis of osteoarthritis and breast cancer and the assessment of pain.…”

“…The sensitivity changes in skin temperature related to specific disorders have been quantified using thermal imaging. [ 7 , 8 ]…”

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“…Mitochondrial dysfunction is known to contribute to the progression of diabetes and diabetes-related complications (13)(14)(15). Since MMA metabolism relies on healthy mitochondria, serum MMA may be a favorable potential marker for predicting adverse clinical outcomes in chronic diseases.…”