Mechanisms of vascular damage in systemic sclerosis

Abstract

Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature.

Long-term Survival of Japanese Patients with Pulmonary Arterial Hypertension Treated with Beraprost Sodium, an Oral Prostacyclin Analogue

“…However, it remains unknown whether these patients with a vasospastic predisposition of the pulmonary arteries are really vasoreactive. In particular, it is likely that vasoreactivity in PAH patients with systemic sclerosis (SSc) is abnormal despite the presence of Raynaud's phenomenon (17). Therefore, such a predisposition is not sufficient to explain our results.…”

Manual lymph drainage improving upper extremity edema and hand function in patients with systemic sclerosis in edematous phase

“…The efficacy of MLD on hand edema in SSc patients may be due to its action on some contributors of SSc tissue edema, such as vasculopathy of blood (14) and lymphatic (9 -11) microvessels, autonomous nervous system activity (15), and inflammatory changes (16). MLD, by stimulating lymphatic vessels (6,8), may contribute to mobilizing edema and removing the excess of interstitial fluid.…”

“…Since the intricate pathogenic pathway of edema in SSc may comprehend microvascular changes (both at blood [14] and lymphatic [11][12][13] vessels), increased sympathetic activity (15), and inflammatory changes (16), we hypothesized that finger and hand edema present in SSc patients might respond to MLD, potentially acting on these aspects.…”

Association of Dermoscopic Profiles of Telangiectases with Nailfold Videocapillaroscopic Patterns in Patients with Systemic Sclerosis

“…The etiology of systemic sclerosis (SSc) remains elusive, but microangiopathy is considered to be significantly associated with disease pathophysiology 1 .…”