Periodic Reporting for period 2 - MINDSHIFT (Mechanistic Integration of vascular aND endocrine pathways for Subtyping Hypertension: an Innovative network approach for Future generation research Training)
Período documentado: 2023-01-01 hasta 2025-03-31
Hypertension is the key determinant of cardiovascular disease and the No.1 ‘silent killer’ worldwide. Despite progress in understanding the causes of hypertension and improvements in clinical management, >85 million people in Europe suffer from cardiovascular disease, costing the EU €210 billion/year. Currently, there is a crucial gap in understanding the dynamic interactions between vascular and endocrine pathways in hypertension. Such knowledge would facilitate redefinition of hypertension subtypes to improve current prevention and treatment.
The overall aim of MINDSHIFT is to improve vascular health management by redefining hypertension subtypes, based on the network dynamics between vascular and endocrine systems. The commensurate specific research objectives were as follows:
• To elucidate inflammatory, metabolic, and fibrotic pathways in vascular pathophysiology of hypertension;
• To characterise (the dynamics of) vascular influences on endocrine derangements;
• To elucidate the mechanistic role of key regulatory endocrine pathways in hypertension;
• To characterise (the dynamics of) endocrine influences on micro- and macrovascular dysfunction;
• To establish a multi-scale and integrative framework to capture, evaluate, and exploit the new understandings.
MINDSHIFT-ITN has fully embraced its network approach, as planned and whilst developing, through the following coherent elements and actions:
• Vascular and Endocrine research had a 50-50% balanced contribution.
• Periodic online and in-person MINDSHIFT meetings, as well as dedicated sessions at conferences in the cardiovascular/hypertension field, facilitated creative interactions between project teams.
• Joint/Double doctorates and related secondments were set up to facilitate new collaboration across the vascular and endocrine research fields.
• MINDSHIFT created a framework for the mechanistic integration of knowledge by promoting the collaborative and collective creative capacity of its community of researchers.
• The professional training track of the ESRs ran in parallel with a supervisors’ track, with events and training, to develop the ITN as a sustainable organization.
• A first-ever formal accreditation by The Recess College for “Partnership Working in Science Networks”, developed through MINDSHIFT but applicable to doctoral training networks.
• At present, a new core group is forming and planning next initiatives to further support the MINDSHIFT ‘Hypertension School’ in the wider science network.
The overall aim of MINDSHIFT is to improve vascular health management by redefining hypertension subtypes, based on the network dynamics between vascular and endocrine systems. The commensurate specific research objectives were as follows:
• To elucidate inflammatory, metabolic, and fibrotic pathways in vascular pathophysiology of hypertension;
• To characterise (the dynamics of) vascular influences on endocrine derangements;
• To elucidate the mechanistic role of key regulatory endocrine pathways in hypertension;
• To characterise (the dynamics of) endocrine influences on micro- and macrovascular dysfunction;
• To establish a multi-scale and integrative framework to capture, evaluate, and exploit the new understandings.
MINDSHIFT-ITN has fully embraced its network approach, as planned and whilst developing, through the following coherent elements and actions:
• Vascular and Endocrine research had a 50-50% balanced contribution.
• Periodic online and in-person MINDSHIFT meetings, as well as dedicated sessions at conferences in the cardiovascular/hypertension field, facilitated creative interactions between project teams.
• Joint/Double doctorates and related secondments were set up to facilitate new collaboration across the vascular and endocrine research fields.
• MINDSHIFT created a framework for the mechanistic integration of knowledge by promoting the collaborative and collective creative capacity of its community of researchers.
• The professional training track of the ESRs ran in parallel with a supervisors’ track, with events and training, to develop the ITN as a sustainable organization.
• A first-ever formal accreditation by The Recess College for “Partnership Working in Science Networks”, developed through MINDSHIFT but applicable to doctoral training networks.
• At present, a new core group is forming and planning next initiatives to further support the MINDSHIFT ‘Hypertension School’ in the wider science network.
Work Package 1 & 2 - Vascular & Endocrine Pathways
WP 1 – An integrated set of pre-clinical and clinical projects showed that chronic low-grade inflammation, metabolic stressors (lipids, methyl-glyoxal) and cellular senescence jointly impair micro- and macro-vascular function in hypertension. Novel imaging metrics and a prototype decision-support algorithm translate these findings into improved risk stratification, while cross-project network analysis revealed shared mechanistic nodes that guided further experimentation. All nine deliverables were completed, with only beneficial scope additions (e.g. diabetes co-models).
WP 2 – Work centred on renin–angiotensin–aldosterone-system dysregulation, uncovering a chromosome-9 miRNA/AOPEP locus, CASZ1–MR signalling, sexually dimorphic adrenal remodelling, and mitochondria-driven Ca²⁺ oscillations as key drivers of aldosterone excess. Adjacent studies showed macrolides exert NO-dependent vasoprotection, PVAT’s early anti-stiffness effect in CKD, and palmitoylation-enhanced NOX5 ROS output. These strands feed into a multi-scale model linking endocrine, oxidative and adipose cues to vascular damage, with no critical deviations from plan.
Work Package 3 - Complementary Training
All basic and advanced network-wide courses were delivered on schedule, giving every ESR the agreed portfolio of scientific-method and transferable-skills training.
Every ESR also completed at least one inter-sector or inter-academic secondment.
The Recess College–led Development Track ran its full sequence of workshops and small-group sessions.
Outputs from these activities, together with updated career plans and formal evidence, in each ESR’s ESR-FOLIO.
Finally, on 12 December 2024 all ESRs were awarded accreditation in “Partnership Working in Science Networks,” confirming that WP3’s training and leadership objectives were fully achieved.
Work Package 4 - Selection & Management
Recruitment and selection, and overall coordination, including risk and contingency management have been achieved. Mid-term check issues have been successfully addressed and no major risks have materialized. Due to unexpected health issue and related project delay, MINDSHIFT got a 3-month extension.
Work Package 5 - Dissemination & Professional Ethics
WP 5 met all its dissemination, exploitation and ethics objectives. A robust outreach infrastructure — website, Twitter, and an ESR-run LinkedIn page that grew organically to 200 followers — supported year-round public-engagement actions such as World Hypertension Day, school science sessions, etc.
Working with industry partners, WP5 delivered exploitation plans and all eleven scheduled deliverables (D5.1-D5.11) on time, the sole change being cancellation of a Bioscientifica special issue when that partner’s leadership changed. Ethics self-assessment, a FAIR-aligned Data Management Plan and end-project policy-feedback reviews confirmed full regulatory compliance and captured best-practice lessons for future European doctoral networks.
WP 1 – An integrated set of pre-clinical and clinical projects showed that chronic low-grade inflammation, metabolic stressors (lipids, methyl-glyoxal) and cellular senescence jointly impair micro- and macro-vascular function in hypertension. Novel imaging metrics and a prototype decision-support algorithm translate these findings into improved risk stratification, while cross-project network analysis revealed shared mechanistic nodes that guided further experimentation. All nine deliverables were completed, with only beneficial scope additions (e.g. diabetes co-models).
WP 2 – Work centred on renin–angiotensin–aldosterone-system dysregulation, uncovering a chromosome-9 miRNA/AOPEP locus, CASZ1–MR signalling, sexually dimorphic adrenal remodelling, and mitochondria-driven Ca²⁺ oscillations as key drivers of aldosterone excess. Adjacent studies showed macrolides exert NO-dependent vasoprotection, PVAT’s early anti-stiffness effect in CKD, and palmitoylation-enhanced NOX5 ROS output. These strands feed into a multi-scale model linking endocrine, oxidative and adipose cues to vascular damage, with no critical deviations from plan.
Work Package 3 - Complementary Training
All basic and advanced network-wide courses were delivered on schedule, giving every ESR the agreed portfolio of scientific-method and transferable-skills training.
Every ESR also completed at least one inter-sector or inter-academic secondment.
The Recess College–led Development Track ran its full sequence of workshops and small-group sessions.
Outputs from these activities, together with updated career plans and formal evidence, in each ESR’s ESR-FOLIO.
Finally, on 12 December 2024 all ESRs were awarded accreditation in “Partnership Working in Science Networks,” confirming that WP3’s training and leadership objectives were fully achieved.
Work Package 4 - Selection & Management
Recruitment and selection, and overall coordination, including risk and contingency management have been achieved. Mid-term check issues have been successfully addressed and no major risks have materialized. Due to unexpected health issue and related project delay, MINDSHIFT got a 3-month extension.
Work Package 5 - Dissemination & Professional Ethics
WP 5 met all its dissemination, exploitation and ethics objectives. A robust outreach infrastructure — website, Twitter, and an ESR-run LinkedIn page that grew organically to 200 followers — supported year-round public-engagement actions such as World Hypertension Day, school science sessions, etc.
Working with industry partners, WP5 delivered exploitation plans and all eleven scheduled deliverables (D5.1-D5.11) on time, the sole change being cancellation of a Bioscientifica special issue when that partner’s leadership changed. Ethics self-assessment, a FAIR-aligned Data Management Plan and end-project policy-feedback reviews confirmed full regulatory compliance and captured best-practice lessons for future European doctoral networks.
MINDSHIFT has re-framed hypertension as a networked, systems disorder by mapping >80 mechanistic links between vascular and endocrine pathways—far exceeding the single-axis studies that dominate the field. This integrative lens, supported by cross-institutional “lab-pairing” and a shared bio-informatics pipeline, has already yielded 29 peer-reviewed papers (including two guideline contributions) and revealed, e.g. (i) inflammatory–metabolic signatures, (ii) key factors of aldosterone biosynthesis, and (iii) novel therapeutic targets.
The consortium has also piloted a seven-phase supervision map and an accredited development track—the first to embed social-science research on mentoring directly into a biomedical doctorate—thereby setting new standards for training quality in European PhD networks. Report "The relationship dynamics of supervision in science: a social research case study from MINDSHIFT-ITN" is available upon negotiation through RecessCollege.org.
Short-term, MINDSHIFT has delivered measurable health benefits—350+ citizens screened during World Hypertension Day events, quarterly patient-education clinics that improve adherence, and STEM outreach that raises application intent among under-represented groups.
Medium-term impacts center on cost-effective risk stratification: earlier detection of primary aldosteronism and inflammation-driven vascular damage could reduce stroke and heart-failure admissions.
The network has also expanded Europe’s skills base, graduating researchers fluent in molecular biology, clinical trial design, data science and entrepreneurial practice. Finally, the supervision-research findings and the new accreditation in “Partnership Working in Science Networks” are informing policy discussions at the European Commission, positioning MINDSHIFT as a model for people-centered, high-impact doctoral ecosystems that can be replicated across disciplines.
The consortium has also piloted a seven-phase supervision map and an accredited development track—the first to embed social-science research on mentoring directly into a biomedical doctorate—thereby setting new standards for training quality in European PhD networks. Report "The relationship dynamics of supervision in science: a social research case study from MINDSHIFT-ITN" is available upon negotiation through RecessCollege.org.
Short-term, MINDSHIFT has delivered measurable health benefits—350+ citizens screened during World Hypertension Day events, quarterly patient-education clinics that improve adherence, and STEM outreach that raises application intent among under-represented groups.
Medium-term impacts center on cost-effective risk stratification: earlier detection of primary aldosteronism and inflammation-driven vascular damage could reduce stroke and heart-failure admissions.
The network has also expanded Europe’s skills base, graduating researchers fluent in molecular biology, clinical trial design, data science and entrepreneurial practice. Finally, the supervision-research findings and the new accreditation in “Partnership Working in Science Networks” are informing policy discussions at the European Commission, positioning MINDSHIFT as a model for people-centered, high-impact doctoral ecosystems that can be replicated across disciplines.