Endotheliopathy in systemic sclerosis: from endothelium-dependent vasodilation to the dysfunction of the vascular reserve, is the paradise lost?

Abstract

Microvascular dysfunction is considered one of the main pathogenetic pathways in systemic sclerosis (SSc), and endothelial cells plays a pivotal role even in the early phases of the disease. Endothelial dysfunction results in an early incapacity to adapt the vascular tone and the blood flow under stress conditions, thus losing the important adaptation mechanism that is the vascular reserve. The loss of vascular tone control in systemic sclerosis is clinically evident as Raynaud’s phenomenon, one of the earliest signs of the disease. An impairment of the vascular reserve has been described in the literature for the main SSc target organs. An alteration of the coronary reserve was shown in SSc asymptomatic patients undergoing a provocative cardiac stress tests. For what concerns the pulmonary circulation, in presence of normal resting pulmonary pressure values in specific subsets of SSc patients subjected to a cycle ergometer test, an abnormal elevation of pulmonary pressure has been showed. Regarding renal arterial circulation, in SSc patients with normal baseline renal function, an absence of improved glomerular filtration after the infusion of a protein load has been demonstrated. Finally, vascular reserve can be altered even in the gastrointestinal circulation as assessed by the study of the splanchnic circulation after a balanced meal. An early detection of an alteration of the physiologic protective mechanism of the vascular reserve could open a “window of opportunity” in which SSc vasculopathy can be potentially reversible, and more responsive to targeted therapeutic strategies.