Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis

Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance

© 2014 The Authors. The angiogenic capability of colorectal carcinomas (CRC), and their susceptibility to anti-angiogenic therapy, is determined by expression of vascular endothelial growth factor (VEGF) isoforms. The intracellular protein T-cell Intracellular Antigen (TIA-1) alters post-transcriptional RNA processing and binds VEGF-A mRNA. We therefore tested the hypothesis that TIA-1 could regulate VEGF-A isoform expression in colorectal cancers. TIA-1 and VEGF-A isoform expression was measured in colorectal cancers and cell lines. We discovered that an endogenous splice variant of TIA-1 encoding a truncated protein, short TIA-1 (sTIA-1) was expressed in CRC tissues and invasive K-Ras mutant colon cancer cells and tissues but not in adenoma cell lines. sTIA-1 was more highly expressed in CRC than in normal tissues and increased with tumour stage. Knockdown of sTIA-1 or over-expression of full length TIA-1 (flTIA-1) induced expression of the anti-angiogenic VEGF isoform VEGF-A 165 b. Whereas flTIA-1 selectively bound VEGF-A 165 mRNA and increased translation of VEGF-A 165 b, sTIA-1 prevented this binding. In nude mice, xenografted colon cancer cells over-expressing flTIA-1 formed smaller, less vascular tumours than those expressing sTIA-1, but flTIA-1 expression inhibited the effect of anti-VEGF antibodies. These results indicate that alternative splicing of an RNA binding protein can regulate isoform specific expression of VEGF providing an added layer of complexity to the angiogenic profile of colorectal cancer and their resistance to anti-angiogenic therapy

Lack of morphometric evidence for ventricular compaction in humans

The remodeling of the compact wall by incorporation of trabecular myocardium, referred to as compaction, receives much attention because it is thought that its failure causes left ventricular non-compaction cardiomyopathy (LVNC). Although the notion of compaction is broadly accepted, the nature and strength of the evidence supporting this process is underexposed. Here, we review the literature that quantitatively investigated the development of the ventricular wall to understand the extent of compaction in humans, mice, and chickens. We queried PubMed using several search terms, screened 1127 records, and selected 56 publications containing quantitative data on ventricular growth. For humans, only 34 studies quantified wall development. The key premise of compaction, namely a reduction of the trabecular layer, was never documented. Instead, the trabecular layer grows slower than the compact wall in later development and this changes wall architecture. There were no reports of a sudden enlargement of the compact layer (from incorporated trabeculae), be it in thickness, area, or volume. Therefore, no evidence for compaction was found. Only in chickens, a sudden increase in compact myocardial thickness layer was reported coinciding with a decrease in trabecular thickness. In mice, morphometric and lineage tracing investigations have yielded conflicting results that allow for limited compaction to occur. In conclusion, compaction in human development is not supported while rapid intrinsic growth of the compact wall is supported in all species. If compaction takes place, it likely plays a much smaller role in determining wall architecture than intrinsic growth of the compact wall

Effect of Sex and Sporting Discipline on LV Adaptation to Exercise

Purpose: Studies assessing female and male athletes indicate that they exhibit qualitatively similar changes compared with sedentary counterparts, but female athletes reveal smaller increases in left ventricular (LV) wall thickness and cavity size compared to male athletes. However, data on gender specific changes in LV geometry in athletes is scarce. We sought to investigate the effect of different types of exercise on LV geometry in a large group of female and male athletes. Methods: 1083 healthy, elite, white athletes (41% females, mean age 21.8 ± 5.7 years) underwent electrocardiogram (ECG) and echocardiogram as part of their cardiovascular evaluation. Sporting disciplines were divided into static, dynamic or mixed. Left ventricular geometry was classified into 4 groups according to relative wall thickness (RWT) and left ventricular mass (LVM) in accordance with the guidelines presented by the European and American Society of Echocardiography : normal (normal LVM/normal RWT), concentric hypertrophy (increased LVM/increased RWT), eccentric hypertrophy (increased LVM/normal RWT), concentric remodelling (normal LVM/increased RWT). Results: Athletes were engaged in 40 different sporting disciplines (62% mixed, 28% dynamic, 10% static) with similar participation rates with respect to the type of exercise between females and males. Females exhibited lower LV mass (83 ± 17 vs 101 ± 21 g/m2, p<0.001) and RWT (0.35 ± 0.05 vs 0.36 ± 0.05, p<0.001) compared to male athletes. Females also demonstrated lower absolute LV dimensions (49 ± 4 vs 54 ± 5 mm, p<0.001) but following correction for BSA the indexed LV dimensions were greater in females (28.6 ± 2.7 vs 27.2 ± 2.7 mm/m2, p<0.001). The majority of athletes showed normal LV geometry (69% of males vs 71% of females, p=0.54). There were no significant gender differences between LV geometry in athletes competing in static or mixed sport, however a greater proportion of females competing in dynamic sport exhibited eccentric hypertrophy compared to males (22% vs 14%, p<0.001). In this subgroup only 4% of females compared to 15% of males demonstrated concentric hypertrophy/remodelling (p<0.001). Conclusions: Highly trained athletes generally show normal LV geometry, however female athletes participating in dynamic sport often exhibit eccentric hypertrophy. Our results indicate that although concentric remodelling or hypertrophy in male athletes engaged in dynamic sport is a relatively common phenotype, it is rare in female athletes and may be a marker of cardiac pathology in a symptomatic athlete