Increased blood levels of transforming growth factor ß in patients with aortic dilatation.

OBJECTIVES: Recent studies have shown that patients with syndromic thoracic aortic aneurysm, particularly patients with bicuspid aortic valve, have increased blood levels of transforming growth factor ß1 (TGF-ß1), indicating this molecule as a prognostic biomarker. However, it is not known whether TGF-ß1 is also elevated in the blood of patients with tricuspid aortic valve and aortic dilatation. METHODS: We analysed the plasma levels of TGF-ß1 in 52 patients with tricuspid or bicuspid aortic valve and with normal or dilated ascending aorta who underwent cardiac surgery in our hospital. RESULTS: TGF-ß1 blood level was significantly increased two-fold in patients with tricuspid aortic valve and dilated aorta compared to patients with tricuspid aortic valve and normal aorta. CONCLUSIONS: Our results suggest that TGF-ß1 blood levels may serve as a prognostic biomarker for patients with syndromic and non-syndromic thoracic aortic aneurysm. Further studies with larger cohorts of patients should be performed to confirm these results.

Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve.

OBJECTIVES: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes. METHODS: Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population. RESULTS: FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found. CONCLUSIONS: BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player.

Selection of reference genes for quantitative real time PCR (qPCR) assays in tissue from human ascending aorta.

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1ß, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

Resident and non-resident stem cells in acute myocardial infarction.

Cardiovascular disease is the leading cause of death in developed countries. Acute myocardial infarction (AMI) is the result of hypoxia leading to cardiomyocyte death. This causes loss of function of contractile tissue, which is replaced by non-contractile fibrous tissue affecting left ventricular ejection fraction (LVEF). One of the current approaches to recover LVEF after an AMI is focused on the search for functional cells to replace the dead tissue, via implantation in the heart of autologous progenitor cells with a regenerative capacity. This review classifies these cells into two types: a) non-resident cells and b) resident cells within the cardiac tissue. We provide an overall view of the various subpopulations and their markers, based, in animal and human models from the early pioneering work to the latest findings.