Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1, T2 and BOLD study

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I ? HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T₂, T₁), hemorrhage (T₂*), vasodilator function (T₂ BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre‐ and post‐contrast T₁) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T₂* values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia‐alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T₂ elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia‐alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high‐risk patients progressing towards heart failure.     

How stiff is skin?

The measurement of the mechanical properties of skin (such as stiffness, extensibility and strength) is a key step in characterisation of both dermal ageing and disease mechanisms and in the assessment of tissue‐engineered skin replacements. However, the biomechanical terminology and plethora of mathematical analysis approaches can be daunting to those outside the field. As a consequence, mechanical studies are often inaccessible to a significant proportion of the intended audience. Furthermore, devices for the measurement of skin function in vivo generate relative values rather than formal mechanical measures, therefore limiting the ability to compare studies. In this viewpoint essay, we discuss key biomechanical concepts and the influence of technical and biological factors (including the nature of the testing apparatus, length scale, donor age and anatomical site) on measured mechanical properties such as stiffness. Having discussed the current state‐of‐the‐art in macro‐mechanical and micromechanical measuring techniques and in mathematical and computational modelling methods, we then make suggestions as to how these approaches, in combination with 3D X‐ray imaging and mechanics methods, may be adopted into a single strategy to characterise the mechanical behaviour of skin.     

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Adiposity and estrogen receptor-positive,postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m² compared to women with BMI 18.5–25 kg/m², the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association.