Mechanistic endotyping of the ROS/cGMP disease cluster in the Estonian Biobank

• DOI: 10.58647/rexpo.23000033.v1
• Publication Date: 2023-10-23T05:20:18Z
• Authors: Cristian Nogales ...; Jaanika Kronberg; Alexandra Petraina; Mayra Pacheco Pac...; Mari Nelis; Lili Milani; Tōnu Esko; Andres Metspalu; Reedik Mägi; Harald H. H. W. S...
• Keywords: Endotype

<p class="first" dir="auto" id="d24259792e205">We hardly comprehend any disease mechanistically, meaning most definitions are organ- and symptom-based fail to represent the underlying mechanism of disease. Current therapies can thus only treat symptoms chronically yielding unprecise low patient-relevant outcomes ( <i>1</i>, <i>2</i>). Symptom-based also have risk agglutinating different molecular mechanisms that cause similar under umbrella terms. As a result, they combined into single common complex entity is impossible untangle with present diagnostic methods. Contrarily, apparently unrelated phenotypes co-occur in same patient beyond chance, which may indicate shared causal <i>3</i>). Thus, order reach precision medicine achieve treatment accuracy, we must first determine endotype patients based on This approach will redefine diseases, shifting focus from affected organs causes <i>4</i>). Here, investigate one best studied diseasome clusters fourteen heterogeneous cardiovascular, neuro-psychiatric, metabolic pulmonary comorbid unmet medical need, defined - at least part by reactive oxygen species <span style="text-decoration: underline">RO</span>S)-induced dysfunction underline">cG</span>MP signaling (ROCG) <i>5</i>, <i>6</i>). Previously, shown NADPH oxidase 5 (NOX5) levels endothelial microparticles were able identify ROCG hypertensive <i>7</i>). used high-throughput screening plasma antibody assay measure NOX5 analyze over 1,000 human samples cluster collaboration Estonian biobank prevalence endotype. Stratifying according both phenotype allow for high precision, i.e., number needed therapeutic interventions. These data show even supposedly endotyping mechanistic re-definition possible.