Automated spatially targeted optical micro proteomics identifies fibroblast- and macrophage-specific regulation of myocardial infarction scar maturation in rats.

Myocardial infarction (MI) results from occlusion of blood supply to the heart muscle causing death of cardiac muscle cells. Following myocardial infarction (MI), extracellular matrix deposition and scar formation mechanically stabilize the injured heart as damaged myocytes undergo necrosis and removal. Fibroblasts and macrophages are key drivers of post-MI scar formation, maturation, and ongoing long-term remodelling; however, their individual contributions are difficult to assess from bulk analyses of infarct scar.

Biomechanical and Mechanobiological Drivers of the Transition From PostCapillary Pulmonary Hypertension to Combined Pre-/PostCapillary Pulmonary Hypertension.

Combined pre-/postcapillary pulmonary hypertension (Cpc-PH), a complication of left heart failure, is associated with higher mortality rates than isolated postcapillary pulmonary hypertension alone. Currently, knowledge gaps persist on the mechanisms responsible for the progression of isolated postcapillary pulmonary hypertension (Ipc-PH) to Cpc-PH. Here, we review the biomechanical and mechanobiological impact of left heart failure on pulmonary circulation, including mechanotransduction of these pathological forces, which lead to altered biological signaling and detrimental remodeling, driving the progression to Cpc-PH.

Sex differences in right ventricular adaptation to pressure overload in a rat model.

With severe right ventricular (RV) pressure overload, women demonstrate better clinical outcomes compared with men. The mechanoenergetic mechanisms underlying this protective effect, and their dependence on female endogenous sex hormones, remain unknown. To investigate these mechanisms and their impact on RV systolic and diastolic functional adaptation, we created comparable pressure overload via pulmonary artery banding (PAB) in intact male and female Wistar rats and ovariectomized (OVX) female rats.

A Comparison of Fiber Based Material Laws for Myocardial Scar.

The mechanics of most soft tissues in the human body are determined by the organization of their collagen fibers. Predicting how mechanics will change during growth and remodeling of those tissues requires constitutive laws that account for the density and dispersion of collagen fibers. Post-infarction scar in the heart, a mechanically and structurally complex material, does not yet have a validated fiber-based constitutive model.

Individual variability in animal-specific hemodynamic compensation following myocardial infarction.

Ventricular enlargement and heart failure are common in patients who survive a myocardial infarction (MI). There is striking variability in the degree of post-infarction ventricular remodeling, however, and no one factor or set of factors have been identified that predicts heart failure risk well. Sympathetic activation directly and indirectly modulates hypertrophic stimuli by altering both neurohormonal milieu and ventricular loading.

Automated Spatially Targeted Optical Microproteomics Investigates Inflammatory Lesions .

Tissue microenvironment properties like blood flow, extracellular matrix, or proximity to immune-infiltrate are important regulators of cell biology. However, methods to study regional protein expression in the native tissue environment are limited. To address this need, we developed a novel approach to visualize, purify, and measure proteins using automated spatially targeted optical microproteomics (AutoSTOMP).

Surgical reinforcement alters collagen alignment and turnover in healing myocardial infarcts.

Previous studies have suggested that the composition and global mechanical properties of the scar tissue that forms after a myocardial infarction (MI) are key determinants of long-term survival, and emerging therapies such as biomaterial injection are designed in part to alter those mechanical properties. However, recent evidence suggests that local mechanics regulate scar formation post-MI, so that perturbing infarct mechanics could have unexpected consequences. We therefore tested the effect of changes in local mechanical environment on scar collagen turnover, accumulation, and alignment in 77 Sprague-Dawley rats at 1, 2, 3 and 6 wk post-MI by sewing a Dacron patch to the epicardium to eliminate circumferential strain while permitting continued longitudinal stretching with each heart beat.