Lipemia poposiłkowa — problem kliniczny i potencjalne miejsce w algorytmach diagnostycznych Stanowisko polskich ekspertów

The following elaboration presents positions of experts from various, mainly European scientific societies regarding utility of postprandial hypertriglyceridemia (HTG) in predicting cardiovascular (CV) risk. New studies and different categories of patients have been included. The following text has been based mainly on 2019 European Society of Cardiology and European Atherosclerosis Society guidelines regarding the management of dyslipidemia, as well as the 2019 international expert panel document. The position of Polish experts on using oral fat tolerance test in clinical practice has also been presented. Remaining problem is to assess potential usefulness of postprandial HTG in estimation of CV risk and to determine whether performing the oral fat tolerance test, that involves consumption of a standard high-fat preparation followed by blood collection at indicated time intervals, can improve CV risk assessment. Although importance of postprandial HTG in the assessment of atherogenic risk is increasingly well documented, there is still need for further research.W poniższym opracowaniu przedstawiono stanowiska ekspertów z różnych towarzystw, głównie europejskich, dotyczące roli hipertriglicerydemii (HTG) poposiłkowej w przewidywaniu ryzyka sercowo-naczyniowego (CV). Uwzględniono nowe badania i różne kategorie pacjentów. Oparto się głównie na wytycznych European Society of Cardiology i European Atherosclerosis Society z 2019 roku, dotyczących postępowania w dyslipidemii, oraz panelu Postprandial hypertriglyceridaemia revisited in era of non-fasting lipid profile testing: a 2019 Expert Panel Statement, main text. Przedstawiono także stanowisko polskich ekspertów stosujących doustny test tolerancji tłuszczów w praktyce klinicznej. Problemem pozostaje ocena roli HTG w szacowaniu ryzyka CV oraz ustalenie, czy spożycie standardowego wysokotłuszczowego preparatu, a następnie pobranie krwi we wskazanym przedziale czasowym, czyli doustny test tolerancji tłuszczów, może poprawić ocenę ryzyka CV. Znaczenie HTG poposiłkowej w ocenie ryzyka aterogennego jest coraz lepiej udokumentowane, jakkolwiek istnieje potrzeba dalszych badań

Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Background To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg). Methodology Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well. Conclusion and significance SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting Cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart

Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

Anterior chamber depth and primary angle-closure glaucoma: an evolutionary perspective

Journal compilation © 2008 Royal Australian and New Zealand College of OphthalmologistsAnterior chamber depth is an inheritable trait which is affected by age, gender and race. Over 30 years ago, Alsbirk proposed that the shallow anterior chamber, which was typical of the Greenlandic Inuit, and which brings the iris in proximity to the cornea, may have evolved as a thermoregulatory adaptation to resist corneal freezing. Here, this hypothesis is revisited. Recent population genetic data which provide evidence for migration patterns of early humans are discussed and the notions of natural selection and ocular adaptation to cold climates are considered. Problems with the hypothesis are examined, but the idea that the shallow anterior chamber has a thermoregulatory role appears sound and suggests that shallow anterior chambers may have evolved in Homo sapiens living in north-east Asia during the last Ice Age.Robert J Casso

Dissociation of Cardiogenic and Postnatal Myocardial Activities of GATA4

Transcription factor GATA4 is a critical regulator of the embryonic and postnatal heart, but the mechanisms and cofactors required for its diverse functions are not fully understood. Here, we show that whereas the N-terminal domain of GATA4 is required for inducing cardiogenesis and for promoting postnatal cardiomyocyte survival, distinct residues and domains therein are necessary to mediate these effects. Cardiogenic activity of GATA4 requires a 24-amino-acid (aa) region (aa 129 to 152) which is needed for transcriptional synergy and physical interaction with BAF60c. The same region is not essential for induction of endoderm or blood cell markers by GATA4, suggesting that it acts as a cell-type-specific transcriptional activation domain. On the other hand, a serine residue at position 105, which is a known target for mitogen-activated protein kinase (MAPK) phosphorylation, is necessary for GATA4-dependent cardiac myocyte survival and hypertrophy but is entirely dispensable for GATA4-induced cardiogenesis. We find that S105 is differentially required for transcriptional synergy between GATA4 and serum response factor (SRF) but not other cardiac cofactors such as TBX5 and NKX2.5. The findings provide new insight into GATA4 mechanisms of action and suggest that distinct regulatory pathways regulate activities of GATA4 in embryonic development and postnatal hearts