Abdominal aortic aneurysm (AAA) is a chronic vascular disease caused by localized weakening and broadening of the abdominal aorta. AAA is a clearly underdiagnosed disease and is burdened with a high mortality rate (65–85%) from AAA rupture. Studies indicate that abnormal regulation of angiogenesis and inflammation contributes to progression and onset of this disease; however, dysregulations in the molecular pathways associated with this disease are not yet fully explained. Therefore, in our study, we aimed to identify dysregulations in the key regulators of angiogenesis and inflammation in patients with AAA in peripheral blood mononuclear cells (using qPCR) and plasma samples (using ELISA). Expression levels of ANGPT1, CXCL8, PDGFA, TGFB1, VEGFB, and VEGFC and plasma levels of TGF-alpha, TGF-beta 1, VEGF-A, and VEGF-C were found to be significantly altered in the AAA group compared to the control subjects without AAA. Associations between analyzed factors and risk factors or biochemical parameters were also explored. Any of the analyzed factors was associated with the size of the aneurysm. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors potentially involved in AAA formation, giving new insight into the molecular pathways involved in the development of this disease and providing candidates for biomarkers that could serve as diagnostic or therapeutic targets.

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.

Varicose veins (VVs) are the most common manifestation of chronic venous disease (CVD) and appear as abnormally enlarged and tortuous superficial veins. VVs result from functional abnormalities in the venous circulation of the lower extremities, such as venous hypertension, venous valve incompetence, and venous reflux. Previous studies indicate that enhanced angiogenesis and inflammation contribute to the progression and onset of VVs; however, dysregulations in signaling pathways associated with these processes in VVs patients are poorly understood. Therefore, in our study, we aimed to identify key regulators of angiogenesis and inflammation that are dysregulated in patients with VVs. Expression levels of 18 genes were analyzed in peripheral blood mononuclear cells (PBMC) using real-time PCR, as well as plasma levels of 6 proteins were investigated using ELISA. Higher levels of CCL5, PDGFA, VEGFC, TGF-alpha, TGF-beta 1, and VEGF-A, as well as lower levels of VEGFB and VEGF-C, were found to be statistically significant in the VV group compared to the control subjects without VVs. None of the analyzed factors was associated with the venous localization of the varicosities. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors in PBMC and plasma from VVs patients, providing new insight into molecular mechanisms that could contribute to the development of VVs and point out promising candidates for circulatory biomarkers of this disease.

Chronic venous disease (CVD) is a common disease caused by hemodynamic disorders of the venous circulation in the lower extremities. The clinical image of this disease is complex and includes such signs as telangiectases, varicose veins, leg edema and skin changes, usually accompanied with ache, pain, tightness, heaviness, swelling and muscle cramps of legs. Venous ulcers develop in the advanced stages of the disease and lead to significant impairment of patient abilities and reduction of the quality of life. CVD is diagnosed based on physical and image examinations, and main treatment options include compression therapy, invasive treatments like endovenous ablation and foam sclerotherapy, as well as pharmacotherapy. Currently, there is no biochemical and molecular biomarkers utilized in diagnosis or treatment of CVD. With regard to this situation, one of the most investigated fields for identification of disease biomarkers is microRNA (miRNA). These constitute a pool of small, non-coding RNAs that play crucial roles in maintaining cellular homeostasis through posttranscriptional regulation of genes expression. Dysregulations of miRNA expression profiles have been found in patients with various diseases, and this situation provides information about potential miRNA signatures involved in pathophysiology. In this review, the studies focused on investigations of miRNA expression patterns in patients with CVD were collected. The performed literature analysis provides contemporary knowledge in the field of miRNA-dependent mechanisms involved in the etiopathogenesis of CVD and shows gaps that need to be filled in further studies.

Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel diagnostic and therapeutic biomarkers. Therefore, in our study, we aimed to identify shared and distinct pathways associated with angiogenesis and inflammation in LEAD, AAA, and VV. The expression of 18 genes in peripheral blood mononuclear cells and the plasma levels of six proteins were compared between groups of 40 patients with LEAD, 40 patients with AAA, and 40 patients with VV. Independent RNA-seq and microRNA-seq data were integrated to predict differentially expressed transcription factors and microRNAs associated with the most significant genes. Gene Ontology functional analysis was performed to determine the potential biological effects of the observed dysregulations. The elevated expression of VEGFB and TGFB1, along with increased plasma levels of VEGF-C and reduced plasma levels of VEGF-A, were distinguishing features of patients with LEAD compared to those with AAA and VV. Decreased plasma levels of TGF-alpha and TGF-beta 1 were found to be indicative of varicose veins compared to individuals with arterial diseases (LEAD and AAA). Transcription factors and microRNAs potentially regulating the obtained signatures were identified and integrated into a hypothetical regulatory network. The observed dysregulations were found to be functionally associated with the response to hypoxia, the positive regulation of angiogenesis, chemotaxis, vascular permeability, and cell adhesion. The presented study identified dysregulations of key angiogenesis- and inflammation-related factors in peripheral blood mononuclear cells and plasma between LEAD, AAA, and VV patients, providing new insights into the shared and distinct molecular mechanisms underlying these diseases.