A pilot shotgun proteomic profiling of peripheral blood mononuclear cells in patients with different MRI phenotypes of cerebral small vessel disease.

Age-related cerebral microangiopathy (CMA) also known as cerebral small vessel disease (CSVD), is a leading cause of cognitive impairment and stroke. Difficulties in studying CSVD are associated with limitations in visualizing small vessels and diagnostics based on MRI signs of brain damage (white matter hyperintensity, lacunae, microbleeds, etc.). Our previous assessment of each CSVD MRI feature using a four-point severity scale and distribution among brain region using cluster analysis revealed the existence of two MRI types. They do not differ in the severity of vascular risk factors but do differ in the severity of clinical manifestations and levels of circulating plasma biomarkers. Here we present results of a pilot panoramic study of the proteome of peripheral blood mononuclear cells from patients with CSVD MRI types I and II, as well as healthy volunteers. CSVD patients showed a tendency toward downregulation of proteins associated with vesicular trafficking and extracellular matrix (ECM) remodeling relative to control values. Patients with CSVD MRI type 1 showed trends toward insufficient activation of protective proteins (arginase-1, thioredoxin, autophagy and protein stress regulators) and excessive activation of platelet proteins and vascular wall remodeling regulators (such as profilin-1), compared to patients with CSVD MRI type 2. These results indicate the need to study the microstructure of the basement membrane, vascular ECM, and perivascular spaces in cerebral small vessels.