Aortic root dilation in associated with the reduction in capillary density observed at nailfold capillaroscopy in SSc patients

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

“…SSc-related vascular abnormalities are particularly evident in the skin, where they can be easily observed by means of nailfold video-capillaroscopy and typically affect the microcirculation, namely capillaries and small blood vessels [ 6 , 19 ]. In particular, affected arterioles and small arteries are characterized by fibrosis of the tunica adventitia, hyperplasia of the tunica media, swelling and thickening of the tunica intima and luminal occlusion, while capillary alterations range from microhemorrhages and giant or distorted capillaries to capillary rarefaction and loss [ 7 , 18 , 20 ].…”

“…Strikingly, intermittent vascular spasm, reperfusion injury and ischemic necrosis are considered to play a pivotal role in inducing myocardial fibrosis, histologically manifesting as a patchy replacement of cardiac myocytes with acellular collagenous material throughout the myocardium [ 4 , 24 , 33 , 34 ]. As far as macrovascular involvement is concerned, arterial intimal thickening and occlusion by atheromatous plaques characterized by a plenty of foamy macrophages and cholesterol clefts with an overlying fibrous cap have been demonstrated in some SSc patients [ 6 , 35 , 36 , 37 ]. Of note, a significant association between aortic root dilation and impairment of capillary density at nailfold video-capillaroscopy was recently detected in a multicenter cohort of SSc patients, suggesting that SSc-related peripheral microangiopathy could mimic that of aortic vasa vasorum [ 6 ].…”

“…As far as macrovascular involvement is concerned, arterial intimal thickening and occlusion by atheromatous plaques characterized by a plenty of foamy macrophages and cholesterol clefts with an overlying fibrous cap have been demonstrated in some SSc patients [ 6 , 35 , 36 , 37 ]. Of note, a significant association between aortic root dilation and impairment of capillary density at nailfold video-capillaroscopy was recently detected in a multicenter cohort of SSc patients, suggesting that SSc-related peripheral microangiopathy could mimic that of aortic vasa vasorum [ 6 ].…”

“…Systemic sclerosis (SSc, or scleroderma) is a multifaceted autoimmune disorder characterized by widespread microvascular abnormalities occurring early during the disease and evolving into a distinctive vasculopathy that inexorably advances in parallel with the development of tissue fibrosis [ 1 , 2 , 3 , 4 ]. The microvascular disease may present clinically as Raynaud’s phenomenon, abnormal nailfold capillaries, digital ulcers, pulmonary arterial hypertension (PAH) and scleroderma renal crisis [ 5 , 6 ] and together with myofibroblast-orchestrated untreatable skin and internal organ fibrosis, often lead to organ failure accounting for the high morbidity and mortality of SSc [ 1 , 2 , 3 ]. Over the past few years, many steps forward have been made in the knowledge of the cellular and molecular mechanisms underlying the unique relationship between SSc-related vasculopathy and fibrosis [ 2 , 3 , 7 ].…”

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients

“…Consistently, our findings ( Figure 1 and Figure 4 ) suggested that SSc could be involved in the pathogenetic chain of arterial stiffening. In this respect, in a previous study [ 38 ], we raised a suggestive hypothesis regarding aortic wall damage in SSc patients. In particular, we found a significant association between nailfold videocapillaroscopy abnormalities and aortic root dilation.…”