Vascular Disease in Scleroderma

Abstract

Although scleroderma is generally considered a fibrosing disease of the tissues, it is now recognized that the underlying vascular disease is playing a fundamental role in its pathogenesis and associated tissue injury. The exact mechanism for the widespread scleroderma vascular disease is still unknown, but endothelial cell injury induced by infection, immune-mediated cytotoxicity, antiendothelial antibodies, and/or ischemia-reperfusion have all been implicated. The downstream effects of blood vessel perturbation produce "biomarkers" of vascular damage that reflect disease and may predict clinical outcomes. A complex interaction between endothelial cells, smooth muscle cells, extracellular matrix, and intravascular circulating factors is now recognized to contribute to the vascular reactivity, remodeling, and occlusive disease of scleroderma. Understanding the mechanisms underlying these processes provides rationale of novel therapeutic strategies and specific targeted therapy. This review will outline some of the evidence for the causes and consequences of scleroderma vascular disease.

Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis

“…The process is systemic and determines multiple clinical manifestations, from the early appearance of Raynaud phenomenon (RP) through the formation of digital ulcers (DU) until severe organ involvement, and impairment of the patient's quality of life with interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), heart involvement, and scleroderma renal crisis, often leading to death 2,3 .…”

Analysis of Laser Speckle Contrast Images Variability Using a Novel Empirical Mode Decomposition: Comparison of Results With Laser Doppler Flowmetry Signals Variability

“…Thus, for pathologies as diabetes or hypertension early microvascular changes have been shown to appear long before organ dysfunctions become clinically manifest (see, e.g., [4], [5]). For systemic sclerosis, burns, flaps, or wounds, skin microvasculature is specifically affected and evoluates with the disease ( [6], [7]). Different optical techniques have become available to monitor microvascular blood flow.…”

Coronary Microvascular Dysfunction in Asymptomatic Patients Affected by Systemic Sclerosis – Limited vs. Diffuse Form –

“…Endothelium dysfunction also results in an imbalance of vasoactive factors, including overproduction of the vasoconstrictor, endothelin-1, and underproduction of the vasodilators, nitric oxide (NO) and prostacyclin. 5 Reduced coronary flow reserve (CFR) can be demonstrated late in the course of the disease in patients with SSc. A severe blunting of CFR, measured invasively during cardiac catheterization, has been demonstrated in patients with diffuse cutaneous SSc with established myocardial involvement and normal coronary angiograms.…”