The athero-contour: A novel tool for global and rapid assessment of atherogenic parameters. A use case in saroglitazar treatment of MAFLD patients.

Background And Aims: Comprehensive assessment of pharmacotherapy effects on atherogenic parameters (AP) that influence the risk of cardiovascular disease (CVD) is challenging due to interactions among a large number of parameters that modulate CVD risk.

Methods: We developed an illustrative tool, athero-contour (AC), which incorporates weighted key lipid, lipo- and glycoprotein parameters, to readily illustrate their overall changes following pharmacotherapy. We demonstrate the applicability of AC to assess changes in AP in response to saroglitazar treatment in patients with metabolic associated fatty liver disease (MAFLD) in the EVIDENCES IV study.

Catheter-Induced Coronary Spasm: Serious But Preventable.

While catheter-induced spasm is considered to be rare, it needs to be ruled out (especially in cases of left main stenosis) to avoid unnecessary revascularization. We present a patient where the underlying tendency for coronary spasm was so high, the severe spasm was possibly the underlying cause of a prior cardiac arrest episode.

SEX AND VASCULAR BIOMECHANICS: A HYPOTHESIS FOR THE MECHANISM UNDERLYING DIFFERENCES IN THE PREVALENCE OF ABDOMINAL AORTIC ANEURYSMS IN MEN AND WOMEN.

The prevalence of abdominal aortic aneurysms differs greatly between men and women across the spectrum of ages. The reason for this discrepancy is not clear and likely involves several factors including the impact of sex hormones. We hypothesize that the unique spatial localization of abdominal aortic aneurysms is dictated in part by local hemodynamic forces on the vascular wall.

Nox4-dependent activation of cofilin mediates VSMC reorientation in response to cyclic stretching.

Vascular smooth muscle cells (VSMCs) are subjected to various types of mechanical forces within the vessel wall. Although it is known that VSMCs undergo cell body reorientation in response to mechanical stimulation, how this mechanical stretch is transduced within the cell into biochemical signals causing cytoskeleton reorganization remains unclear. Cofilin, a protein that controls actin dynamics, is activated by Slingshot phosphatase-dependent serine 3 dephosphorylation by redox-dependent mechanisms.

Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness.

Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why.

Maximal stimulation-induced in situ myosin light chain kinase activity is upregulated in fetal compared with adult ovine carotid arteries.

Postnatal decreases in vascular reactivity involve decreases in the thick filament component of myofilament calcium sensitivity, which is measured as the relationship between cytosolic calcium concentration and myosin light chain (MLC20) phosphorylation. The present study tests the hypothesis that downregulation of thick filament reactivity is due to downregulation of myosin light chain kinase (MLCK) activity in adult compared with fetal arteries. Total MLCK activity, calculated as %MLC20 phosphorylated per second in intact arteries during optimal inhibition of myosin light chain phosphatase activity, was significantly less in adult (6.

Inhibition of myosin light-chain phosphorylation inverts the birefringence response of porcine airway smooth muscle.

Muscle birefringence, caused mainly by parallel thick filaments, increases in smooth muscle during stimulation, signalling thick filament formation upon activation. The reverse occurs in skeletal muscle, where a decrease in birefringence has been correlated with crossbridge movement away from the thick filaments. When force generation by trachealis muscle was inhibited with wortmannin, which inhibits myosin light-chain phosphorylation and thick-filament formation, but not the calcium increase caused by stimulation, the birefringence response inverted, suggesting crossbridge movement similar to that of skeletal muscle.

Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle.

Birefringence and force produced by pig tracheal smooth muscles were recorded every 100 ms during electrically stimulated tetani at muscle lengths that varied 1.5-fold and at the peak of acetylcholine contractures at the same lengths. Isometric force was nearly the same at all lengths.