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Updated: Apr 21, 2026
Author Spotlight: A Pharmacodissection Approach to Uncover Mechanisms in Cardiovascular Disease Risk Populations
Published on: July 21, 2023
Endothelial dysfunction is present only in the microvasculature and microcirculation of early diffuse systemic
R T Domsic1, C Dezfulian, Al Shoushtari
1Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. rtd4@pitt.edu.
Objectives:
To evaluate endothelial function and vascular stiffness in large, medium, small and microcirculatory blood vessels in very early diffuse systemic sclerosis (SSc).
Methods:
We studied consecutive early diffuse SSc patients, defined as <2 years from first SSc symptom who did not have a prior cardiovascular event. Age, gender and race-matched controls were recruited. All underwent assessment of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) brachial flow-mediated dilation (FMD), digital peripheral artery tonometer (EndoPAT) assessment and laser speckle contrast imaging (LSCI).
Results:
Fifteen early diffuse SSc and controls were evaluated. The average age was 49 years, 63% were female and 93% were Caucasian. There were no differences in body mass index, hypertension, diabetes or hyperlipidaemia between controls and SSc patients. Mean SSc disease duration was 1.3 years. In the large central vessels, there was no difference in aortic PWV (p=0.71) or carotid IMT (p=0.92) between SSc patients and controls. Similarly, there was no difference in endothelial dysfunction with brachial artery FMD after ischaemia (p=0.55) and nitroglycerin administration (p=0.74). There were significantly lower values for digital EndoPAT measures (p=0.0001) in SSc patients. LSCI revealed a distinct pattern of microcirculatory abnormalities in response to ischaemia in SSc patients compared to controls. Imaging demonstrated a blunted microcirculatory hyperaemia of the hand with greater subsequent response to nitroglycerin.
Conclusions:
These findings suggest that the earliest endothelial changes occur in smaller arterioles and microvascular beds, but not in medium or macrovascular beds, in early diffuse SSc.
