Fetal programming as the cause of all the evils in adult humans: atherosclerosis and coronary heart disease included

〈 Collection 2020/3 About us Imprint Open access Editorial board Contact Vision and mission Services Picture credits Disclaimer Congresses Job vacancies For readers Subscription Current issue Archives Search For authors Guidelines Copyright Submission Article types Supplements For advertisers Media data Portfolio Reader poll Reprints Offer Sales team Collection 2020/3 REVIEW ARTICLE Fetal programming as the cause of all the evils in adult humans: atherosclerosis and coronary heart disease included DOI: https://doi.org/10.4414/cvm.2020.02113 Publication Date: 11.06.2020 Cardiovasc Med. 2020;23:w02113 Balistreri Carmela R. Affiliationskeyboard_arrow_down Summary The theory of David Barker on “the fetal origin of adult diseases” is revolutionising the pathophysiology and aetiopathogenesis of adult human diseases such as atherosclerosis. Atherosclerosis and related coronary heart diseases (CHDs) appear to be the result of fetal programming, with the cardiovascular system, and particularly the endothelium component, being the principal target of this process. This suggests that cardiovascular diseases can take place during fetal development. This life period is crucial for developmentally programming body systems (such as the cardiovascular system), their ageing and disease. A sophisticated interplay of exogenous-gestational environmental factors with the fetal genome induces epigenetic changes (microRNA, DNA methylation patterns and histone structure alterations) and expression of altered phenotypes of developing systems. A poor maternal diet rich in cholesterol, diabetes, obesity, smoking and exposure to various environmental pollutants represent the major factors related to an increased risk and progression of atherosclerosis in postnatal life. The fetal cardiovascular system is susceptible to these factors, and developmental programming events cause endothelial dysfunction, small coronary arteries, stiffer vascular tree, fewer cardiomyocytes, coagulopathies and atherogenic blood lipid profiles in the fetus. Consequently, preventive interventions are recommended for both parents who want to have children, for counteracting the onset of atherosclerosis and CHDs in new generations

Abstracts of the 3rd Joint Meeting of Pathology and Laboratory Medicine

Background: Degenerative forms of mitral valve diseases (MVDs) are complex pathologies. Thus, it is difficult to make generalizations about MVD pathways or genetic risk factors. However, a key role of metalloproteinases (MMPs) in their pathophysiology is emerging. Thus, we performed a study to assess eventual associations of some functional SNPs in MMP-2 and MMP-9 genes with MVD risk, symptom severity and short- and long-term (4.8 years) complications. Methods: For this purpose, 90 patients and two control groups were genotyped for MMP-2 and MMP-9 gene SNPs, and systemic levels of proatrial natriuretic peptide (ANP), and two enzymes were quantified and correlated to the MMP-2 and MMP-9 SNPs. In addition, associations between these SNPs and symptom severity and short- and long-term complications were evaluated. Results: Interestingly, rs3918242 MMP-9 and rs2285053 MMP-2 SNPs were significantly represented in cases compared to two control groups, and were associated with a higher MVD risk. Cases stratified for New York Heart Association (NYHA) symptoms, and particularly NYHA III+IV, with rs3918242 CT+TT MMP-9 and rs2285053CT+TT genotypes also showed higher severity related to significant higher systemic levels of MMP enzymes and pro-ANP at enrollment and 4.8-year follow-up times. In addition, cases with these genotypes, and particularly NYHAIII+IV, had a very significant percentage of complications, particularly at the 4.8-year follow-up. Surprisingly, 20% of patient controls developed MVD at 4.8- year follow-up and were carriers of these genotypes. Conclusions: The associations observed seem to suggest that the two SNPs might represent useful biomarkers and targets for preventing and monitoring MVDs, leading to a more appropriate management and outcom

The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases

Obesity is an energy-rich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress. It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells. As consequence, increased circulating levels of proinflammatory cytokines, hormone-like molecules, and other inflammatory markers are induced. This determines a chronic active inflammatory condition, associated with the development of the obesity-related inflammatory diseases. This paper describes the role of adipose tissue and the biological effects of many adipokines in these diseases

Is it the time of seno-therapeutics application in cardiovascular pathological conditions related to ageing?

It rates that in 2030, the cardiovascular diseases (CVD) will result in 40% of all deaths and rank as the leading cause. Thus, the research of appropriate therapies able to delay or retard their onset and progression is growing. Of particular interest is a new branch of the medical science, called anti-ageing medicine since CVD are the result of cardiovascular ageing. Senescent cells (SC) accumulate in cardiovascular system contributing to the onset of typical age-related cardiovascular conditions (i.e., atherosclerosis, medial aorta degeneration, vascular remodeling, stiffness). Such conditions progress in cardiovascular pathologies (i.e., heart failure, coronary artery disease, myocardial infarction, and aneurysms) by evocating the production of a proinflammatory and profibrotic senescence-associated secretory phenotype (SASP). Consequently, therapies able to specifically eliminate SC are in developing. The senotherapeutics represents an emerging anti-SC treatment, and comprises three therapeutic approaches: (a) molecules to selectively kill SC, defined senolytics; (b) compounds able in reducing evocated SC SASP, acting hence as SASP suppressors, or capable to change the senescent phenotype, called senomorphics; (c) inhibition of increase of the number of SC in the tissues. Here, it describes them and the emerging data about current investigations on their potential clinical application in CVD, stressing benefits and limitations, and suggesting potential solutions for applying them in near future as effective anti-CVD treatment

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

: Aorta diseases, such as ascending aorta aneurysm (AsAA), are complex pathologies, currently defined as inflammatory diseases with a strong genetic susceptibility. They are difficult to manage, being insidious and silent pathologies whose diagnosis is based only on imaging data. No diagnostic and prognostic biomarkers or markers of outcome have been known until now. Thus, their identification is imperative. Certainly, a deep understanding of the mechanisms and pathways involved in their pathogenesis might help in such research. Recently, the key role of oxidative stress (OS) on the pathophysiology of aorta disease has emerged. Here, we describe and discuss these aspects by revealing some OS pathways as potential biomarkers, their underlying limitations, and potential solutions and approaches, as well as some potential treatments

On the Road to Accurate Biomarkers for Cardiometabolic Diseases by Integrating Precision and Gender Medicine Approaches

The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent valid disease surrogates and well-fitted CMD biomarkers. To address this challenge, data from multi-omics types (genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and nutrigenomics), from human and animal models, have become available. However, individual omics types only provide data on a small part of molecules involved in the complex CMD mechanisms, whereas, here, we propose that their integration leads to multidimensional data. Such data provide a better understanding of molecules related to CMD mechanisms and, consequently, increase the possibility of identifying well-fitted biomarkers. In addition, the application of gender medicine also helps to identify accurate biomarkers according to gender, facilitating a differential CMD management. Accordingly, the impact of gender differences in CMD pathophysiology has been widely demonstrated, where gender is referred to the complex interrelation and integration of sex (as a biological and functional marker of the human body) and psychological and cultural behavior (due to ethnical, social, and religious background). In this review, all these aspects are described and discussed, as well as potential limitations and future directions in this incipient field

Genotyping of Sex Hormone-Related Pathways in Benign and Malignant Human Prostate Tissues: Data of a Preliminary Study

Prostate cancer (PCa) is a major health issue in Westernized countries, representing a common cause of morbidity and mortality in the elderly male population. Endogenous sex steroids, along with environmental factors (notably diet) and host immune and inflammatory responses, are likely to cooperate in the pathogenesis of the disease. Based on the assumption that a complex endocrine–inflammatory-immune interaction is primarily implicated in human PCa, we have investigated the interplay between sex steroids and inflammation in development and growth of human PCa. To this end, we have assessed nine functional single nucleotide polymorphisms (SNP)s of five genes involved in sex hormone-related pathways in both hyperplastic and malignant human prostate tissues, as well as in matched controls and in a ‘‘supercontrol’’ group composed of male Sicilian centenarians. In particular, the following genes were investigated: AR-OMIM313700, SRD5A2-NM-000348, CYP19-NM-031226, ERS1-NM-001122742, ERS2-NM-001040276. A significant association with prostate cancer was found in seven out of the nine SNPs considered. Although this is a preliminary study and larger investigations are needed to confirm the role of these genes in PCa development and/or progression, our data might provide an experimental basis to develop additional or alternative strategies for prevention and treatment of PCa

A promising therapeutic peptide and preventive/diagnostic biomarker for age-related diseases: The Elabela/Apela/Toddler peptide

Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations

NF-κB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies.

Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion sustains that during evolution the host defense and ageing process have become linked together. Thus, the large array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to characterize biological age and, since age is a major risk factor in many degenerative diseases, could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological ageing, providing ideas on eventual working hypothesis about potential targets for the development of new therapeutic strategies and improving, as consequence, the quality of life of elderly populatio