The authors have declared that no competing interests exist.
Cardiovascular disease is actually a major cause of mortality, illness and hospitalization worldwide. Several risk factors have been identified that are strongly associated with the development of cardiovascular disease. Public prevention strategies have relied predominately on managing environmental factors that contribute to cardiovascular disease, such as obesity, smoking and lack of exercise. The understanding of the role of genetics in cardiovascular disease development has become much more important to link genetics with the onset of disease and response to therapy. This seeks to examine how genes can predispose individuals to cardiovascular disease and how this knowledge might be applied to more comprehensive preventive strategies in the future. In addition, the review explores possibilities for genetics in cardiovascular disease treatment, particularly through the use of identified driver genes and gene therapy. To fully understand the biological implications of these associations, there is a need to relate them to the exquisite, multilayered regulation of protein expression and regulatory elements, mutation, microRNAs and epigenetics. Understanding how the information contained in the DNA relates to the operation of these regulatory layers will allow us not only to better predict the development of cardiovascular disease but also to develop more effective therapies.
Cardiovascular diseases (CVDs) are a group of diseases of the heart and blood vessels. CVDs are the leading cause of death worldwide
The pathogenesis of CVDs is complex, influenced by genetic, environmental and lifestyle factors
Epigenetics has been initially studied in CVD patientsfor its prominent role in inflammationand vascular involvement
Even though substantial advances in medical management, prognosis of CVD remains poor, and identification of mechanisms and potential therapeutic approaches are still a priority of considerable importance
However, studies of CVD heritability are confounded by the fact that several other risk factors, such as blood pressure, lipid levels and diabetes, are themselves under genetic control
CVDs are studied in a mechanistic, genetic and biochemical contexts that include genomic
· To review research findings and facts on regulation mechanisms of candidate genes for human cardiovascular diseases
· To review nature and prevalence of cardiovascular diseases and its types for human.
The most prevalent CVDs include ischaemic heart disease (heart attack), cerebrovascular disease (stroke), hypertension, inflammatory heart disease and rheumatic heart disease in that order of prevalence
Cardiovascular disease includes coronary artery diseases (CAD) such asangina and myocardial infarction (commonly known as a heart attack)
CHD is one of CVD which is the most common type of birth defect, affecting 1% of all live births, and is the leading non-infectious cause of death in the first year of life
In humans, heart development begins at 15 to 16 days of gestation with the migration of precardiac stem cells, in five steps:(1) migration of precardiac cells from the primitive streak and assembly of the paired cardiac crescents at the myocardial plate, (2) coalescence of the cardiac crescents to form the primitive heart tube, establishing the definitive heart, (3) cardiac looping, assurance of proper alignment of the future cardiac chambers, (4) septation and heart chambers formation, and (5) development of the cardiac conduction system and coronary vasculature
The establishment of left-right asymmetry is very important to the normal development of heart
Specific genes such as the NOTCH receptor, Jagged (JAG), WNT, transforming growth factor beta 2 (TGF ß2) and bone morphogenic proteins have been implicated in cardiac neural crest development in the mouse
Mutation in FBN1gene encoding extracellular matrix protein fibrillin 1, responsible for Marfan’s syndrome
However, more recent studies suggest that microfibrils normally bind the large latent complex of the cytokine transforming growth factor β (TGF-β) and that failure of this event to occur results in increased TGF-β activation and signaling. Now, investigators are exploring the hypothesis that blocking TGF-β signaling will ameliorate the growth of aortic aneurysms in Marfan’s syndrome.
For further examples of therapeutic approaches derived from the study of Mendelian disorders, we refer the reader to a recent review on this topic
Rare mutations in FBN1cause the thoracic aortic aneurysms and dissections seen in Marfan’s syndrome, whereascommon SNPs in the introns of FBN1are the top association result in a GWAS for spontaneous, non-syndromic thoracic aortic aneurysm and dissection
PTPRC, FYB and FCER1G have been identified as key drivers of an inflammatory gene signature underlying multiple diseases (including CAD)
MEF2A disease-causing gene for CAD and MI is highly expressed in the endothelium susceptible to inflammation and the formation of an atherosclerotic plaque, which may result in thrombosis, MI, and sudden death
Familial combined hyperlipidemia (FCHL) is present in patients of CAD which is elevated serum total cholesterol or triglycerides.
The work that reported a positive association between a mutation of human ANP gene and the risk of stroke
There are associations of migraine and stroke with NOS3, EDN and EDNRB regulatory genes
Some findings have been reported that HDAC9associated with large vessel disease
Polymorphisms within the promoter region of the FCN2 gene are associated with plasma levels of this protein in chronic RHD patients and probably prolong the time of infection or repeated streptococcal infections
The interleukin 1 (IL-1) gene cluster located on chromosome 2 includes the genes expressing the proinflammatory cytokines IL-1a and IL-1b and their inhibitor IL-1 receptor antagonist (IL-1RA). The ratio of IL-1RA to IL-1 is important in determining the duration and intensity of the inflammatory response
Mannose-binding lectin is encoded by
It is shown that dilated cardiomyopathy tissues contain elevated levels of p53 and its regulators MDM2 and HAUSP compared to non-failing hearts
Inhibition of SMAD2 phosphorylation preserves cardiac function during pressure overload
Heart development is controlled by a highly conserved network of transcription factors that connect signaling pathways with genes of muscle growth, patterning, and contractility. The core transcription factor network consists of NKX2, MEF2, GATA, TBX
In mammals, four Notch family receptors have been described: NOTCH1 up to NOTCH4; Notch ligands are encoded by the Jagged (JAG1 and JAG2) and Delta-like (DLL1, DLL3 and DLL4) gene families
The formation of bicuspid aortic valve might reflect the role of Notch signaling in regulating the epithelial-mesenchymal transition required for the generation of the heart valves
MicroRNAs are natural, single-stranded, non–protein-coding small RNA molecules (~22 nucleotides) that regulate gene expression by binding to target mRNAs and suppress its translation or initiate its degradation
Epigenetics refers to DNA and chromatin modifications that play a critical role in regulation of various genomic functions, cell differentiation and embryonic morphogenesis
Cardiovascular diseases are very important to control since it causes high mortality and morbidity. Gene prediction by different molecular markers such as SNP in genomics, proteomics level that has identified important new genes involved in various forms of cardiovascular disease. Biological validation and medical exploitation of this predictions, as well as characterization of key mechanisms responsible for disease formation and progression, are subjects of future research.