MitOConexão: Investigando o Nexo Mitocondrial em Onco-Cardiologia

SMART General Objective Specific: Strengthen scientific and technological capacities in Northern Portugal by investigating mitochondrial dysfunction as a central pathological mechanism in BC and CVD. The project aims to advance precision medicine and translational research, developing novel, low-cost approaches for remote CV monitoring in BC patients. Measurable: Generate new knowledge, establish clinically actionable biomarkers, and validate targeted strategies that reduce the dual burden of BC and CVD. Achievable: Leverage robust research infrastructures, cutting-edge molecular profiling methods, and strong clinical collaborations to ensure effective project execution and real-world applicability. Relevant: Address critical health challenges in cardio-oncology and personalized medicine. Time-Bound: Deliver key research outputs, technological platforms, and knowledge-transfer activities within 36 months, reinforcing national and regional innovation priorities and ensuring sustained impact. Specific Objectives 1. Characterize Mitochondrial Epigenetic Markers in BC Patients With and Without CVD Identify and quantify mitochondrial epigenetic markers (e.g., 5hmC, HMGB1) in BC tissue and peripheral blood. o Rationale: Through techniques such as immunohistochemistry (IHC), including multiplex IHC, ELISA, and RT-qPCR, differentiate the epigenetic signatures of BC patients with versus without CVD. o Expected Outcome: Provide clinically relevant biomarkers for better patient stratification and inform therapies that target mitochondrial dysfunction. 2. Investigate Macrophage Profiling in Immune Modulation, Cardiovascular Remodeling, and Tumor Progression Examine the role of tumor-associated macrophages (TAMs), starting with CD163+ subsets, within BC and correlate infiltration profiles with CVD and oncologic outcomes. o Rationale: Depending on initial findings, the profiling will be expanded to include additional polarization and functional markers (e.g., CD68, CD206, HLA-DR, iNOS) to refine the characterization of TAM subtypes and their roles in tumor progression and CV remodeling. o Expected Outcome: Reveal macrophage phenotypic patterns associated with disease trajectory and identify potential immunomodulatory targets for therapeutic intervention, particularly in BC patients at increased CVD risk. 3. Analyze Mitochondrial Stress Markers (Parkin, BNIP3, MnSOD) Linked to Cancer-Driven Cardiovascular Dysfunction Assess the expression of key mitochondrial stress markers in BC patients deemed at risk for CV dysfunction. o Rationale: Combine clinically annotated patient cohorts with advanced mitochondrial profiling to detect stress signatures predictive of CV injury in cancer contexts. o Expected Outcome: Establish risk models that integrate BC severity with markers of mitochondrial distress, enabling proactive clinical management. 4. Identify Biomarkers Predictive of Cardiovascular and Cancer Risks Through Remote Monitoring Implement a cost-effective, long-term monitoring strategy using dried blood spots (DBS) and related methodologies o Rationale: Compare DBS-assessed markers (e.g., cardiac troponins, NT-proBNP, IL-1, CRP) with gold-standard plasma measurements in BC patients, thereby reducing hospital visits and allowing real-time risk assessment. o Expected Outcome: Generate a prognostic model to forecast both CV events and cancer progression, optimizing clinical decision-making while reducing healthcare costs.