Congenital heart diseases (CHDs) are recognized as the most common type of birth malformations. Although recent advances in pre- and neonatal diagnosis as well as in surgical procedures have reduced the morbidity and mortality for many CHD, the etiology for CHD remains undefined. In non-syndromic and isolated (without a familial history or a Mendelian inheritance) forms of CHDs, a multifactorial pathogenesis with interplay between inherited and non-inherited causes is recognized. In this paper, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal cardiac development in non-syndromic and isolated CHD, including mutations in cardiac transcription factors, the role of somatic mutations and epigenetic alterations as well as the influence of gene-environment interactions. In the near future, the advent of high-throughput genomic technologies with the integration of system biology will expand our understanding of isolated, non-syndromic CHDs for their prevention, early diagnosis and therapy.

Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays)....

Aging is one of the main risk factors for cardiovascular disease, resulting in a progressive organ and cell decline. This study evaluated a possible joint impact of two emerging hallmarks of aging, leucocyte telomere length (LTL) and common mitochondrial DNA deletion (mtDNA⁴⁹⁷⁷), on major adverse cardiovascular events (MACEs) and all-cause mortality in patients with coronary artery disease (CAD). We studied 770 patients (673 males, 64.8 ± 8.3 years) with known or suspected stable CAD. LTL and mtDNA⁴⁹⁷⁷ deletion were assessed in peripheral blood using qRT-PCR. During a median follow-up of 5.4 ± 1.2 years, MACEs were 140 while 86 deaths were recorded. After adjustments for confounding risk factors, short LTLs and high mtDNA⁴⁹⁷⁷ deletion levels acted independently as predictors of MACEs (HR: 2.2, 95% CI: 1.2–3.9, p = 0.01 and HR: 1.7, 95% CI: 1.1–2.9, p = 0.04; respectively) and all-cause mortality events (HR: 2.1, 95% CI: 1.1–4.6, p = 0.04 and HR: 2.3, 95% CI: 1.1–4.9, p = 0.02; respectively). Patients with both short LTLs and high mtDNA⁴⁹⁷⁷ deletion levels had an increased risk for MACEs (HR: 4.3; 95% CI: 1.9–9.6; p = 0.0006) and all-cause mortality (HR: 6.0; 95% CI: 2.0–18.4; p = 0.001). The addition of mtDNA⁴⁹⁷⁷ deletion to a clinical reference model was associated with a significant net reclassification improvement (NRI = 0.18, p = 0.01). Short LTL and high mtDNA⁴⁹⁷⁷ deletion showed independent and joint predictive value on adverse cardiovascular outcomes and all-cause mortality in patients with CAD. These findings strongly support the importance of evaluating biomarkers of physiological/biological age, which can predict disease risk and mortality more accurately than chronological age.