The Relationship of Left Ventricular Diastolic Dysfunction and Asymmetrical Dimethylarginine as a Biomarker of Endothelial Dysfunction with Cardiovascular Risk Assessed by Systematic Coronary Risk Evaluation2 Algorithm and Heart Failure-A Cross-Sectional Study.

Background: Cardiovascular (CV) risk factors, causing endothelial dysfunction (ED) and left ventricular diastolic dysfunction (LVDD), contribute to an increased risk of heart failure (HF). The aim of this study was to determine the relationship between the occurrence of LVDD and ED with CV risk assessed by the Systematic Coronary Risk Evaluation2 (SCORE2) algorithm and HF. Methods: In the period from November 2019 to May 2022, a cross-sectional study that included 178 middle-aged adults was conducted. Transthoracic echocardiography (TTE) was used to assess left ventricular (LV) diastolic and systolic function. ED was assessed using the plasma values of asymmetric dimethylarginine (ADMA) and was determined using the ELISA method. Results: The majority of subjects with LVDD grades 2 and 3 had high/very high SCORE2, developed HF and all were taking medication (p < 0.001). They also had significantly lowest plasma ADMA values (p < 0.001). We found that the reduction of ADMA concentration is influenced by certain groups of drugs, or more significantly, by their combinations (p < 0.001). Conclusions: In our study, we confirmed a positive correlation between LVDD, HF and SCORE2 severity. The results showed a negative correlation between the biomarkers of ED, LVDD severity, HF, and SCORE2, which we believe is due to medication effects.

Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly.

Mitotic spindle assembly is crucial for chromosome segregation and relies on bundles of microtubules that extend from the poles and overlap in the middle. However, how these structures form remains poorly understood. Here we show that overlap bundles arise through a network-to-bundles transition driven by kinetochores and chromosomes. STED super-resolution microscopy reveals that PRC1-crosslinked microtubules initially form loose arrays, which become rearranged into bundles. Kinetochores promote microtubule bundling by lateral binding via CENP-E/kinesin-7 in an Aurora B-regulated manner. Steric interactions between the bundle-associated chromosomes at the spindle midplane drive bundle separation and spindle widening. In agreement with experiments, theoretical modeling suggests that bundles arise through competing attractive and repulsive mechanisms. Finally, perturbation of overlap bundles leads to inefficient correction of erroneous kinetochore-microtubule attachments. Thus, kinetochores and chromosomes drive coarsening of a uniform microtubule array into overlap bundles, which promote not only spindle formation but also chromosome segregation fidelity.