Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise. Patients with SSc and controls were similar in body stature, handgrip strength, and MAP; however, brachial artery blood flow at rest was nearly twofold lower in patients with SSc compared with controls (22 ± 4 vs. 42 ± 5 ml/min, respectively; P < 0.05). Additionally, SSc patients had an ∼18% smaller brachial artery lumen diameter with an ∼28% thicker arterial wall at rest ( P < 0.05). Although, during handgrip exercise, there were no differences in MAP between the groups, exercise-induced hyperemia and therefore vascular conductance were ∼35% lower at all exercise workloads in patients with SSc ( P < 0.05). Brachial artery vasodilation, as assessed by the relationship between Δbrachial artery diameter and Δshear rate, was significantly attenuated in the patients with SSc ( P < 0.05). Finally, vascular dysfunction in the patients with SSc was accompanied by elevated blood markers of oxidative stress and attenuated endogenous antioxidant activity ( P < 0.05). Together, these findings reveal attenuated exercise-induced brachial artery blood flow and conduit arterial vasodilatory dysfunction during handgrip exercise in SSc and suggest that elevated oxidative stress may play a role.
MicroRNA-30c attenuates fibrosis progression and vascular dysfunction in systemic sclerosis model mice
