Cardiac FGF23: new insights into the role and function of FGF23 after acute myocardial infarction.

OBJECTIVE: We aimed to elucidate the local role of FGF23 after myocardial infarction in a mouse model induced by left anterior descending artery (LAD) ligation. APPROACH AND RESULTS: (C57BL/6 N) mice underwent MI via LAD ligation and were sacrificed at different time-points post MI. The expression and influence of FGF23 on fibroblast and macrophages was also analyzed using isolated murine cells. We identified enhanced cardiac FGF23 mRNA expression in a time-dependent manner with an early increase, already on the first day after MI. FGF23 protein expression was abundantly detected in the infarcted area during the inflammatory phase. While described to be primarily produced in bone or macrophages, we identified cardiac fibroblasts as the only source of local FGF23 production after MI. Inflammatory mediators, such as IL-1ß, IL-6 and TNF-α, were able to induce FGF23 expression in these cardiac fibroblasts. Interestingly, we were not able to detect FGF23 at later time points after MI in mature scar tissue or remote myocardium, most likely due to TGF-ß1, which we have shown to inhibit the expression of FGF23. We identified FGFR1c to be the most abundant receptor for FGF23 in infarcted myocardium and cardiac macrophages and fibroblasts. FGF23 increased migration of cardiac fibroblast, as well as expression of Collagen 1, Periostin, Fibronectin and MMP8. FGF23 also increased expression of TGF-ß1 in M2 polarized macrophages. CONCLUSION: In conclusion, cardiac fibroblasts in the infarcted myocardium produce and express FGF23 as well as its respective receptors in a time-dependent manner, thus potentially influencing resident cell migration. The transitory local expression of FGF23 after MI points towards a complex role of FGF23 in myocardial ischemia and warrants further exploration, considering its role in ventricular remodeling.

Apolipoprotein E in Cardiovascular Diseases: Novel Aspects of an Old-fashioned Enigma.

The presence of different APOE isoforms represents a well-known risk factor for cardiovascular diseases. Besides the pleiotropic effects of APOE polymorphism on heart and neurological diseases, this review summarizes the less-known functions of APOE and the possible implications for cardiovascular disorders. Beyond the role as lipid transporting protein, its involvement in lipid membrane homeostasis and signaling, as well as its nuclear transcriptional effects suggests a more complex role of APOE, receiving great interest from researchers and physicians from all medical fields. Due to the presence of different APOE isoforms in human population, understanding APOE's role in pathological processes represents not only a challenge, but a demand for further development of therapeutic strategies for cardiovascular diseases.

Artificial Intelligence versus Doctors' Intelligence: A Glance on Machine Learning Benefaction in Electrocardiography.

Computational machine learning, especially self-enhancing algorithms, prove remarkable effectiveness in applications, including cardiovascular medicine. This review summarizes and cross-compares the current machine learning algorithms applied to electrocardiogram interpretation. In practice, continuous real-time monitoring of electrocardiograms is still difficult to realize. Furthermore, automated ECG interpretation by implementing specific artificial intelligence algorithms is even more challenging. By collecting large datasets from one individual, computational approaches can assure an efficient personalized treatment strategy, such as a correct prediction on patient-specific disease progression, therapeutic success rate and limitations of certain interventions, thus reducing the hospitalization costs and physicians' workload. Clearly such aims can be achieved by a perfect symbiosis of a multidisciplinary team involving clinicians, researchers and computer scientists. Summarizing, continuous cross-examination between machine intelligence and human intelligence is a combination of precision, rationale and high-throughput scientific engine integrated into a challenging framework of big data science.

Nano-level morphology of scar tissue after myocardial infarction.

Atomic force microscopy (AFM) is a pioneer imaging technique commonly employed by biological researchers in detection of the properties of biological membranes over the last decade. The AFM findings distinguish its applicability from the conventional methods, such as: confocal, multi-photons, electron microscopy, etc. as well as from the mechanical methods (compression and indentation test, extensiometry, etc.). With its high resolution (below 10 nm), AFM has emerged as a powerful tool in obtaining the nanostructural details and biomechanical properties of heart tissue. The composition of extracellular matrix is essential for heart compliance and its mechanical function. Here, we illustrate the surface morphology, its structural assembling and the mechanical properties of a myocardial infarction scar section aquired via AFM, in dry conditions. The cross section through the mature myocardial scar of mice after myocardial infarction shows that the embedded fibrils into the tissue matrix of a mature scar overlap at some sites, and form network-like structures. The nano-fibrils surface shows defined structural periodicity. A cross-section along the axial fibrilar direction gives an average D-periodic banding pattern of approximately 50,3 nm (± 6,2 nm std.). As future perspective, yet uncovered morphological and mechanical investigations, correlated with functional studies, open a new window for understanding pathological mechanisms.