The Predictive Role of Proteomics in Blood Pressure Response of Hypertensive Patients Undergoing Renal Denervation.

Hypertension (HTN) is the most prevalent modifiable risk factor associated with cardiovascular morbidity and mortality, while its prevalence is rising globally. Despite the availability of safe and effective antihypertensive medication, in a large proportion of patients, blood pressure (BP) control to guideline-recommended targets is not achieved. The current knowledge is that sympathetic nervous system hyperactivity contributes to initiation, maintenance and progression of HTN.

Renal denervation (RDN) is a minimally invasive catheter-based method dedicated to disrupt renal sympathetic enervation using different ablation techniques, while is the most extensively investigated device-based therapy for ΗΤΝ. Current endovascular catheter systems access renal arteries and deliver radiofrequency energy, ultrasound energy or use neurotoxic agents such as alcohol, resulting in destruction of the peri-arterial afferent and efferent renal nerves. RDN has experienced ups and downs as a potential treatment option for HTN over recent years of investigation. The initial proof-of-concept, open label clinical trials produced promising results about RDN effectiveness in BP lowering, although, the first randomized sham-controlled trial failed to confirm the previous encouraging results. However, the latest randomized, sham-controlled trials with improved design and methodology demonstrated significant reductions in office blood pressure (OBP) and ambulatory blood pressure (ABP) in patients undergoing RDN. Despite demonstrated efficacy and safety of RDN procedure, about 30% to 40% of patients do not present with a clinically significant BP reduction, even in latest optimally designed clinical trials. This might be due to the pathophysiological substrate in these patients, while identifying a biomarker of BP response could result in a better selection of patients with better response.

The dynamic role of proteins to support the life is documented since the initial stages of biological research. The proteome can be defined as the overall protein content of a biological system such as cell, tissue, biological fluid, etc. Proteomics is the large-scale study of the proteome, as well as the identification and quantification of these proteins. There are some basic steps of proteomic analysis: sample acquisition, protein extraction, protein separation, protein sequence determination and protein identification with bioinformatic techniques in referential databases. Chromatography based techniques are used for protein extraction and high-resolution two-dimensional electrophoresis techniques for proteins separation, while mass spectrometry (MS)-based analysis is widely applied for the protein sequence determination. Proteomic analysis is used in various research settings in detecting diagnostic biomarkers and highlighting pathogenicity mechanisms, alteration of expression patterns in response to different signals or interpretation of functional protein pathways in different diseases. The ultimate goal of proteomics is to better comprehend the molecular complexity while establishing diagnostic and therapeutic healthcare algorithms for the prevention and treatment of diseases.

Α. Aim of the study:

The main purpose of this study is to investigate the potential predictive role of the urine proteomics in BP response of patients undergoing RDN. This hypothesis may lead to the emergence of biomarkers in urine of hypertensive patients in order to optimally select those who will undergo RDN procedure.