Daily Cardiology Research Analysis

-Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, with post-infarction cardiac remodeling, particularly excessive scar formation, representing a critical determinant of patient outcomes. However, the mechanistic pathways governing pathological scar formation remain incompletely understood. Here, we demonstrate that ADAMTS1 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 1), significantly upregulated in endothelial cells (ECs) following MI, plays a pivotal role in regulating cardiac fibroblast activation through a novel mechanotransduction pathway involving integrin α8 (ITGα8). Using EC-specific ADAMTS1 overexpression and knockout mice combined with cardiac fibroblast-specific ITGα8 deletion models, we found that ADAMTS1 overexpression exacerbates cardiac dysfunction and increases scar size, while ADAMTS1 deficiency provides cardioprotection. Mechanistically, ADAMTS1 modulates extracellular matrix stiffness through proteoglycan (PG) cleavage rather than direct protein interactions, which activates ITGα8 mechanosensing specifically in cardiac fibroblasts. Among integrin family members tested, ITGα8 shows selective responsiveness to ADAMTS1-mediated mechanical cues, as confirmed by tunable-stiffness hydrogel experiments and validated through comprehensive proteomic and functional analyses. ITGα8 deficiency rescues ADAMTS1-induced cardiac dysfunction and reduces pathological scar formation. These findings reveal a previously unrecognized ADAMTS1-ITGα8 mechanotransduction pathway, representing a promising therapeutic target for optimizing post-infarction cardiac remodeling.

Proteomic technologies have advanced our understanding of disease mechanisms, patient stratification and targeted therapies. However, applying cardiac proteomics in translational research requires overcoming the barrier of tissue accessibility. Formalin-fixed, paraffin-embedded (FFPE) heart tissue, widely preserved in pathology collections, remains a largely untapped resource. Here we demonstrate that proteomic profiles are well preserved in FFPE human heart specimens and compatible with high-resolution, quantitative analysis. Quantifying approximately 4,000 proteins per sample, we show this approach effectively distinguishes disease states and subanatomical regions, revealing distinct underlying protein signatures. Specifically, the human sinoatrial node exhibited enrichment of collagen VI and G protein-coupled receptor signaling. Myocardial biopsies from patients with arrhythmogenic cardiomyopathy were characterized by fibrosis and metabolic/cytoskeletal derangements, clearly separating them from donor heart biopsies. This study establishes FFPE heart tissue as a robust resource for cardiac proteomics, enabling retrospective molecular profiling at scale and unlocking archived specimens for disease discovery and precision cardiology.

AIMS: The Framingham Risk Score (FRS), a tool primarily used for atherosclerotic cardiovascular disease (ASCVD) risk stratification, incorporates factors like age, obesity, and smoking. However, its role in predicting cancer and heart failure (HF) risk remains unclear, while emerging data suggest these two conditions coincide frequently. METHODS: We conducted a post-hoc analysis using data from the PREVEND study and validated our findings in the UK Biobank. We examined the association between FRS tertiles at baseline and incident cancer or HF. Fine-Gray regression models were used to calculate subdistribution hazard ratios (sHRs), adjusting for estimated glomerular filtration rate and urinary albumin excretion with all-cause mortality as a competing risk. RESULTS: In PREVEND, we included 8123 participants (mean age 49±13 years, 50% female). Over follow-up periods of 17.46 years (IQR 17.15-17.80) years (cancer) and 23.39 years (IQR 13.78-23.81) years (HF), 1176 participants developed new-onset cancer, and 758 developed new-onset HF. In a multivariable analysis, participants in the highest FRS tertile compared to the lowest had a higher hazard for both cancer (sHR 2.32, p<0.001) and HF (sHR 10.08, p<0.001). Participants in the highest FRS tertile had the worst survival (log-rank p<0.001). We validated these findings in the UK Biobank (N=389942) wherein individuals in the highest FRS tertile also had a higher hazard for both cancer (sHR 2.05, p<0.001) and HF (sHR 5.99, p<0.001) compared to the lowest tertile. CONCLUSION: The FRS associates with new-onset cancer or HF, implicating a broader clinical application of the FRS beyond ASCVD-risk stratification in cardio-oncology. Heart disease and cancer are the two most common causes of death worldwide. They are usually treated as separate problems, but research shows they can be connected. For example, some cancer treatments can damage the heart, and people with heart problems may also have a higher risk of cancer. In this study, we looked at whether a simple heart health score -the Framingham Risk Score (FRS) -can also help predict who might get cancer or heart failure in the future. This score is usually used to estimate a person’s risk of heart disease over 10 years. We used health data from two large groups of people: one from the Netherlands (PREVEND) and one from the UK (UK Biobank), following them for up to 23 years. We found that people with a high FRS were more likely to develop both cancer and heart failure compared to those with a low score. This means the FRS could be useful not just for predicting heart problems, but also for spotting people at higher risk of serious illnesses like cancer. Doctors could then take early steps like lifestyle changes, better treatment of blood pressure or cholesterol, and more regular health checks to help prevent these diseases. Our study suggests that looking at heart and cancer risks together could lead to better care and prevention in the future.