{"doi":"10.1093/ajh/hpaf034","title":"Integrating Proteomics and Mendelian Randomization to Identify New Therapeutic Targets","abstract":"Hypertension is a major risk factor for cardiovascular disease, stroke, renal failure, and other end-organ damage. It is estimated that over 1.4 billion people worldwide suffer from hypertension, with a significant portion remaining undiagnosed or inadequately treated. The pathophysiology of hypertension is multifaceted, involving complex interactions between genetic, environmental, and physiological factors that influence vascular resistance, cardiac output, and sodium homeostasis. At the core of hypertension is increased systemic vascular resistance, primarily driven by endothelial dysfunction, arterial stiffness, and vascular remodeling.1 The endothelium plays a key role in maintaining vascular homeostasis by regulating vasodilation, inflammatory responses, and thrombosis. Dysfunction in endothelial signaling pathways—characterized by reduced nitric oxide bioavailability, increased oxidative stress, and chronic low-grade inflammation—contributes to sustained hypertension.2 The renin-angiotensin-aldosterone system is another fundamental pathway implicated in hypertension. Angiotensin II, the key effector molecule of this system, promotes vasoconstriction, sodium retention, and inflammation, exacerbating blood pressure elevation and vascular damage. Beyond classical mechanisms, emerging evidence highlights the role of immune dysregulation and metabolic disturbances in hypertension.3,4 Chronic low-grade inflammation, driven by immune cell infiltration into vascular tissues and upregulation of pro-inflammatory cytokines, exacerbates vascular dysfunction and increases blood pressure.5","journal":"American Journal of Hypertension","year":2025,"id":539025,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640421,"name":"Fahimeh Varzideh","orcid":"0000-0003-2423-0831","position":1,"is_corresponding":false},{"id":363775,"name":"Urna Kansakar","orcid":"0000-0001-5847-0521","position":2,"is_corresponding":false},{"id":490256,"name":"Stanislovas S. Jankauskas","orcid":"0000-0002-0843-5098","position":3,"is_corresponding":false},{"id":635008,"name":"Scott Wilson","orcid":"0000-0001-5436-5863","position":4,"is_corresponding":false},{"id":497601,"name":"Pasquale Mone","orcid":"0000-0001-6267-5845","position":5,"is_corresponding":false},{"id":225561,"name":"Gaetano Santulli","orcid":"0000-0001-7231-375X","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:52:25.799399Z","pmid":"40083258","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}