Biomarkers and mechanisms of early vascular damage

MRI Types of Cerebral Small Vessel Disease and Circulating Markers of Vascular Wall Damage

“…The established role of TNF-α-mediated reactions in the formation of type 2 MRI changes is consistent with research data showing that white matter damage is not just a consequence of chronic hypoxia, but is caused and maintained by a pro-inflammatory environment [61]. Previously, we established an association between TNF-α and WMH in younger patients with signs of cSVD on MRI, which was unrelated to hypertension, leading to the hypothesis that TNF-α-mediated reactions play an independent role in the development of early-onset cSVD [22]. The potential link with MRI type 2 in the subsequent development of mixed dementia cannot be ruled out.…”

“…The pathophysiology of cSVD has not been completely established [8,16,17]. Therefore, it is especially important to improve the MRI-based diagnosis of cSVD and to study the mechanisms of its development [7,[18][19][20], to identify the pathophysiological markers of disease progression, for example, by assessing the relationship between MRI data and the blood parameters associated with various mechanisms of vessel and brain damage [16,[21][22][23]. We hypothesized that a sequential analysis of MRI signs severity in various parts of the brain and their combination will be able to reveal groups (clusters) of MRI signs, most likely because of differences in their pathogenesis.…”

“…In this way, comparing clusters of MRI signs with circulating markers of vascular and cerebral damage can help to differentiate the pathogenetic variants of cSVD and the associated clinical manifestations. We studied tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor 1-α (HIF-1α), and vascular endothelial growth factor-A (VEGF-A), which were linked with the presence of MRI signs of cSVD in a previous screening study of individuals of working age with and without hypertension [22]. Moreover, these factors were chosen because experimental evidence showed their involvement in the leading mechanisms of cSVD development-damage of the endothelium and extracellular matrix with subsequent remodeling of the vascular wall-as well as the role of chronic inflammation accompanied by high vascular wall permeability in initiating and maintaining these processes [24][25][26][27].…”

A Scoping Review on Biomarkers of Endothelial Dysfunction in Small Vessel Disease: Molecular Insights from Human Studies

“…Conversely, a study with 100 patients of recent cortical or lacunar ischaemic stroke failed to find a significant relationship between plasma t-PA concentrations and PVS count or volume after adjusting for age, sex and vascular risk factors [73]. No association was found between PAI-1 levels and WMH volume or the presence of lacunes in 651 community-based elderly participants or in 71 SVD patients and 21 healthy controls [108,109].…”

“…Lacunar stroke patients (n = 65) had higher levels of t-PA 1-3 months post-stroke compared to cortical stroke patients (n = 60) after adjusting for age, sex and vascular risk factors, perhaps indicating a role in the development or progression of mechanisms specific to SVD [70]. Dobrynina et al [108] also reported a significant positive correlation between t-PA levels and WMH severity and PVS burden in 71 SVD patients and 21 healthy controls; however, they did not adjust for potential clinical covariates in this study. Conversely, a study with 100 patients of recent cortical or lacunar ischaemic stroke failed to find a significant relationship between plasma t-PA concentrations and PVS count or volume after adjusting for age, sex and vascular risk factors [73].…”