Chapters authored
Genetic Factors Underlying Susceptibility to Acute Pyelonephritis and Post-infectious Renal Damage
Part of the book: Recent Advances in the Field of Urinary Tract Infections
Involvement of the Renin‐Angiotensin System in Atherosclerosis
The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).
Part of the book: Renin-Angiotensin System
Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development
During the last decade, quantitative measurement of the methylation status in white blood cells (WBCs) has been used as a potential biomarker in a variety of diseases. Long interspersed nucleotide element-1 (LINE-1) has been used widely as a surrogate marker of global DNA methylation. Altered maternal DNA methylation is suggested to be an underlying mechanism in the trisomy 21 and the development of birth defects, including congenital heart defects (CHDs). The molecular mechanisms that underlie the epigenetic regulation of gene transcription are independent of DNA sequence, but they do depend on environmental stimuli, which are especially important in fetal development in utero environment. Folic acid deficiency and genetic variations of folate pathway genes, such as the methylenetetrahydrofolate reductase gene (MTHFR), are foremost among these maternal risk factors. Also, there are exogenous risk factors (cigarette smoking, alcohol intake, medication use, periconceptional maternal supplementation, body mass index, and dietary habits) with impact on maternal LINE-1 methylation. MTHFR C677T genotype/diet and other environmental factors as significant predictors of LINE-1 DNA methylation in regard to congenital diseases will be discussed in the chapter.
Part of the book: DNA Methylation Mechanism