Critical limb ischemia (CLI) of the lower extremities is a severe form of peripheral arterial disease (PAD) characterized by a markedly reduces blood flow supply to the legs. In many cases the blood perfusion is dramatically worsened by episodes of embolization from complicated or unstable arterial plaques. The hypoperfusion heavily affect the functional performance of the limb muscles causing atrophy and functional exhaustion. In CLI, repetitive cycles of ischemia/reperfusion are a source of tissue damage. In reperfusion stage, the overproduction of mitochondrial reactive oxigen species due to the uncoupling of the respiratory chain trigger the inflammatory response involved in the development of vascular functional and structural damage related to atherosclerosis. Mitochondrial impairment is moreover considered a pivotal cause of muscular atrophy and myopathy associated with critical leg ischemia.
The relevance of monitoring oxidative stress and mitochondrial dysfunction in cardiovascular diseases (CVDs) is corroborated by a consistent correlation between degree of oxidative stress and severity of CVDs and of its complications. The dual role of circulating mononuclear cells (PBMCs), both as a marker of disease conditions and as a direct contributor to disease progression has been established. PBMCs circulate in the blood stream and can distribute and amplify oxidative stress in the vascular system. Also, acting as a reporter of oxidative stress status, they might be useful to understand the mechanisms involved in the pathogenesis of vascular diseases and to reflect the impact of therapeutic interventions.
Based on that, we will verify whether the PBMCs may represent a tool (i) to detect a possible oxidative status related to PAD and in particularly to CLI (ii) to verify the involvement of mitochondrial impairment as a contributory mechanism in the progression of PAD to CLI, (iii) to screen the PAD patients experiencing worsening ischemia.
