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The Impact of Aging on Cardio and Cerebrovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 59042

Special Issue Editor

Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of Salerno, Salerno, Italy
Interests: cardiologia; Ipertensione arteriosa

Special Issue Information

Dear Colleagues,

In the last few decades, the aged population affected by cardio- and cerebrovascular diseases (CVD) has been increasing. Obviously, several physiological and pathological mechanisms are involved in the progression of an unsuccessful ageing, but the alteration of the vascular system and unfavorable genetic profiles represent common traits of the unhealthy ageing.

Although several improvements in the treatment of cardio- and cerebrovascular diseases in elderly populations have been made to increase survival, many of these fail, and several molecular mechanisms remain unclear. Thus, more studies are still needed to understand the best management options to improve therapeutic outcomes and promote healthy aging.

We invite scientists and researchers contribute original research articles, as well as review articles, which reflect the progress of elucidating the mechanisms and new pathways hidden behind successful aging, highlighting the interplay of vasculature and longevity-associated genes.

We welcome all articles that describe new and important findings on the role of the cardiovascular system in disease or aging. The submission of manuscripts that allow an expansion of knowledge and that describe new strategies to treat or prevent the pathological status of unsuccessful aging are welcome.

Potential topics include, but are not limited to, the following:

  • New mechanisms involved in the healthy progression of aging: The role of cardio- and cerebrovascular diseases.
  • Recent advances in cellular and molecular aspects of mechanisms, therapies, or prevention of vascular diseases and age-related diseases.
  • New possible genes involved in successful aging: New promising perspectives for the lengthening of life.
  • Studies directed to find and develop new possible drugs for the prevention of chronic and aging-related diseases.
  • Identification of new age-related biomarkers: An alternative approach to monitoring and preventing an unsuccessful aging process.

Prof. Dr. Carmine Vecchione
Guest Editor

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Keywords

  • Cardiovascular diseases
  • cerebrovascular diseases
  • aging
  • longevity genes
  • molecular mechanisms

Published Papers (10 papers)

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Research

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11 pages, 10233 KiB  
Article
Delayed Onset of Age-Dependent Changes in Ultrastructure of Myocardial Mitochondria as One of the Neotenic Features in Naked Mole Rats (Heterocephalus glaber)
by Lora Bakeeva, Valeria Vays, Irina Vangeli, Chupalav Eldarov, Susanne Holtze, Thomas Hildebrandt and Vladimir Skulachev
Int. J. Mol. Sci. 2019, 20(3), 566; https://doi.org/10.3390/ijms20030566 - 29 Jan 2019
Cited by 7 | Viewed by 4498
Abstract
In this study, the ultrastructure of mitochondria in cardiomyocytes of naked mole rats (Heterocephalus glaber) aged from 6 months to 11 years was examined. Mitochondria in cardiomyocytes of naked mole rats have a specific ultrastructure that is different from those in [...] Read more.
In this study, the ultrastructure of mitochondria in cardiomyocytes of naked mole rats (Heterocephalus glaber) aged from 6 months to 11 years was examined. Mitochondria in cardiomyocytes of naked mole rats have a specific ultrastructure that is different from those in cardiomyocytes of other mammalian species studied to date. In contrast to mitochondria of other mammalian cardiomyocytes, where the internal space is completely filled by tightly packed parallel rows of cristae, mitochondria in cardiomyocytes of naked mole rats have a chaotic pattern of cristae organization with wave-like contours. Gradual formation of mitochondrial ultrastructure occurs in naked mole rats for many years. Two mitochondrial populations are developed to the age of 5 years. In addition to the main population, there are some large organelles which exceed normal sizes by two to three times. Most cristae in these mitochondria are assembled into small groups, which form the curved and ring-like structures. The appearance of some specific structural changes (i.e. bundles of parallel cristae) is observed in the mitochondrial population of naked mole rat after 11 years of age. However, these bundles are very rare and of sporadic nature. Morphometric analysis has shown that the superficial density of the inner mitochondrial membrane is similar in all examined age groups of naked mole rats: 21.1 at 6 months; 23.21 at 3 years; 23.55 at 5 years; and 20.8 at 11 years. This level is almost two times lower than in other animals studied (mice and rats). The data demonstrate that pathological changes in mitochondrial apparatus are not present in naked mole rats at least until the age of 11 years. The mitochondrial apparatus corresponds to the phenotype in young animals, thus being another neotenic feature in naked mole rats. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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16 pages, 3206 KiB  
Article
NOX Inhibition Improves β-Adrenergic Stimulated Contractility and Intracellular Calcium Handling in the Aged Rat Heart
by Álvaro Valdés, Adriana V. Treuer, Guillermo Barrios, Nikol Ponce, Roberto Fuentealba, Raul A. Dulce and Daniel R. González
Int. J. Mol. Sci. 2018, 19(8), 2404; https://doi.org/10.3390/ijms19082404 - 15 Aug 2018
Cited by 7 | Viewed by 3762
Abstract
Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide [...] Read more.
Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart, [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. For this we used adults (≈5 month-old) and aged (20–24 month-old) rats. Contractility was evaluated in isolated hearts, challenged with isoproterenol. To assess [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced in aged myocytes (p < 0.05), and was further reduced by apocynin. NOX2 expression along with NADPH oxidase activity was increased in aged hearts. Phospholamban phosphorylation (Ser16/Thr17) after isoproterenol treatment was reduced in aged hearts compared to adults and was restored by apocynin treatment (p < 0.05). In conclusion, β-adrenergic-induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca2+ handling proteins and myofilaments. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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Review

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16 pages, 490 KiB  
Review
Age-Dependent Myocardial Dysfunction in Critically Ill Patients: Role of Mitochondrial Dysfunction
by Andrew J. Lautz and Basilia Zingarelli
Int. J. Mol. Sci. 2019, 20(14), 3523; https://doi.org/10.3390/ijms20143523 - 18 Jul 2019
Cited by 3 | Viewed by 3637
Abstract
Myocardial dysfunction is common in septic shock and post-cardiac arrest but manifests differently in pediatric and adult patients. By conventional echocardiographic parameters, biventricular systolic dysfunction is more prevalent in children with septic shock, though strain imaging reveals that myocardial injury may be more [...] Read more.
Myocardial dysfunction is common in septic shock and post-cardiac arrest but manifests differently in pediatric and adult patients. By conventional echocardiographic parameters, biventricular systolic dysfunction is more prevalent in children with septic shock, though strain imaging reveals that myocardial injury may be more common in adults than previously thought. In contrast, diastolic dysfunction in general and post-arrest myocardial systolic dysfunction appear to be more widespread in the adult population. A growing body of evidence suggests that mitochondrial dysfunction mediates myocardial depression in critical illness; alterations in mitochondrial electron transport system function, bioenergetic production, oxidative and nitrosative stress, uncoupling, mitochondrial permeability transition, fusion, fission, biogenesis, and autophagy all may play key pathophysiologic roles. In this review we summarize the epidemiologic and clinical phenotypes of myocardial dysfunction in septic shock and post-cardiac arrest and the multifaceted manifestations of mitochondrial injury in these disease processes. Since neonatal and pediatric-specific data for mitochondrial dysfunction remain sparse, conclusive age-dependent differences are not clear; instead, we highlight what evidence exists and identify gaps in knowledge to guide future research. Finally, since focal ischemic injury (with or without reperfusion) leading to myocardial infarction is predominantly an atherosclerotic disease of the elderly, this review focuses specifically on septic shock and global ischemia-reperfusion injury occurring after resuscitation from cardiac arrest. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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22 pages, 688 KiB  
Review
Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart
by Shanna Hamilton and Dmitry Terentyev
Int. J. Mol. Sci. 2019, 20(10), 2386; https://doi.org/10.3390/ijms20102386 - 14 May 2019
Cited by 58 | Viewed by 9101
Abstract
Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and increased propensity for arrhythmias, with the risk of sudden cardiac death significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as [...] Read more.
Aging of the heart is associated with a blunted response to sympathetic stimulation, reduced contractility, and increased propensity for arrhythmias, with the risk of sudden cardiac death significantly increased in the elderly population. The altered cardiac structural and functional phenotype, as well as age-associated prevalent comorbidities including hypertension and atherosclerosis, predispose the heart to atrial fibrillation, heart failure, and ventricular tachyarrhythmias. At the cellular level, perturbations in mitochondrial function, excitation-contraction coupling, and calcium homeostasis contribute to this electrical and contractile dysfunction. Major determinants of cardiac contractility are the intracellular release of Ca2+ from the sarcoplasmic reticulum by the ryanodine receptors (RyR2), and the following sequestration of Ca2+ by the sarco/endoplasmic Ca2+-ATPase (SERCa2a). Activity of RyR2 and SERCa2a in myocytes is not only dependent on expression levels and interacting accessory proteins, but on fine-tuned regulation via post-translational modifications. In this paper, we review how aberrant changes in intracellular Ca2+ cycling via these proteins contributes to arrhythmogenesis in the aged heart. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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13 pages, 869 KiB  
Review
Regenerative Capacity of Endogenous Factor: Growth Differentiation Factor 11; a New Approach of the Management of Age-Related Cardiovascular Events
by Luc Rochette, Alexandre Meloux, Eve Rigal, Marianne Zeller, Yves Cottin, Gabriel Malka and Catherine Vergely
Int. J. Mol. Sci. 2018, 19(12), 3998; https://doi.org/10.3390/ijms19123998 - 12 Dec 2018
Cited by 8 | Viewed by 4440
Abstract
Aging is a complicated pathophysiological process accompanied by a wide array of biological adaptations. The physiological deterioration correlates with the reduced regenerative capacity of tissues. The rejuvenation of tissue regeneration in aging organisms has also been observed after heterochronic parabiosis. With this model, [...] Read more.
Aging is a complicated pathophysiological process accompanied by a wide array of biological adaptations. The physiological deterioration correlates with the reduced regenerative capacity of tissues. The rejuvenation of tissue regeneration in aging organisms has also been observed after heterochronic parabiosis. With this model, it has been shown that exposure to young blood can rejuvenate the regenerative capacity of peripheral tissues and brain in aged animals. An endogenous compound called growth differentiation factor 11 (GDF11) is a circulating negative regulator of cardiac hypertrophy, suggesting that raising GDF11 levels could potentially treat or prevent cardiac diseases. The protein GDF11 is found in humans as well as animals. The existence of endogenous regulators of regenerative capacity, such as GDF11, in peripheral tissues and brain has now been demonstrated. It will be important to investigate the mechanisms with therapeutic promise that induce the regenerative effects of GDF11 for a variety of age-related diseases. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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18 pages, 965 KiB  
Review
Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives
by Rita Del Pinto and Claudio Ferri
Int. J. Mol. Sci. 2018, 19(12), 3701; https://doi.org/10.3390/ijms19123701 - 22 Nov 2018
Cited by 50 | Viewed by 6910
Abstract
Low-grade chronic inflammation is a common denominator in atherogenesis and related diseases. Solid evidence supports the occurrence of an impairment in the innate and adaptive immune system with senescence, favoring the development of acute and chronic age-related diseases. Cardiovascular (CV) diseases (CVD), in [...] Read more.
Low-grade chronic inflammation is a common denominator in atherogenesis and related diseases. Solid evidence supports the occurrence of an impairment in the innate and adaptive immune system with senescence, favoring the development of acute and chronic age-related diseases. Cardiovascular (CV) diseases (CVD), in particular, are a leading cause of death even at older ages. Inflammation-associated mechanisms that contribute to CVD development include dysregulated redox and metabolic pathways, genetic modifications, and infections/dysbiosis. In this review, we will recapitulate the determinants and consequences of the immune system dysfunction at older age, with particular focus on the CV system. We will examine the currently available and potential future strategies to counteract accelerated CV aging, i.e., nutraceuticals, probiotics, caloric restriction, physical activity, smoking and alcohol cessation, control of low-grade inflammation sources, senolytic and senescence-modulating drugs, and DNA-targeting drugs. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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14 pages, 1209 KiB  
Review
A Model of Evolutionary Selection: The Cardiovascular Protective Function of the Longevity Associated Variant of BPIFB4
by Francesco Villa, Albino Carrizzo, Anna Ferrario, Anna Maciag, Monica Cattaneo, Chiara Carmela Spinelli, Francesco Montella, Antonio Damato, Elena Ciaglia and Annibale Alessandro Puca
Int. J. Mol. Sci. 2018, 19(10), 3229; https://doi.org/10.3390/ijms19103229 - 19 Oct 2018
Cited by 13 | Viewed by 4960
Abstract
Evolutionary forces select genetic variants that allow adaptation to environmental stresses. The genomes of centenarian populations could recapitulate the evolutionary adaptation model and reveal the secrets of disease resistance shown by these individuals. Indeed, longevity phenotype is supposed to have a genetic background [...] Read more.
Evolutionary forces select genetic variants that allow adaptation to environmental stresses. The genomes of centenarian populations could recapitulate the evolutionary adaptation model and reveal the secrets of disease resistance shown by these individuals. Indeed, longevity phenotype is supposed to have a genetic background able to survive or escape to age-related diseases. Among these, cardiovascular diseases (CVDs) are the most lethal and their major risk factor is aging and the associated frailty status. One example of genetic evolution revealed by the study of centenarians genome is the four missense Single Nucleotide Polymorphisms (SNPs) haplotype in bactericidal/permeability-increasing fold-containing family B, member 4 (BPIFB4) locus that is enriched in long living individuals: the longevity associated variant (LAV). Indeed, LAV-BPIFB4 is able to improve endothelial function and revascularization through the increase of endothelial nitric oxide synthase (eNOS) dependent nitric oxide production. This review recapitulates the beneficial effects of LAV-BPIFB4 and its therapeutic potential for the treatment of CVDs. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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19 pages, 1126 KiB  
Review
The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation
by Albino Carrizzo, Carmine Izzo, Marco Oliveti, Antonia Alfano, Nicola Virtuoso, Mario Capunzo, Paola Di Pietro, Mariaconsiglia Calabrese, Eros De Simone, Sebastiano Sciarretta, Giacomo Frati, Serena Migliarino, Antonio Damato, Mariateresa Ambrosio, Francesco De Caro and Carmine Vecchione
Int. J. Mol. Sci. 2018, 19(10), 2968; https://doi.org/10.3390/ijms19102968 - 28 Sep 2018
Cited by 50 | Viewed by 6836
Abstract
Diabetes mellitus is a common disease that affects 3–5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6–8% of the population. Of great concern is that the number of cases of [...] Read more.
Diabetes mellitus is a common disease that affects 3–5% of the general population in Italy. In some countries of northern Europe or in North America, it can even affect 6–8% of the population. Of great concern is that the number of cases of diabetes is constantly increasing, probably due to the increase in obesity and the sedentary nature of the population. According to the World Health Organization, in the year 2030 there will be 360 million people with diabetes, compared to 170 million in 2000. This has important repercussions on the lives of patients and their families, and on health systems that offer assistance to patients. In this review, we try to describe in an organized way the pathophysiological continuity between diabetes mellitus, endothelial dysfunction, and platelet hyperaggregation, highlighting the main molecular mechanisms involved and the interconnections. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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24 pages, 5205 KiB  
Review
Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia
by Michela Ferrucci, Francesca Biagioni, Larisa Ryskalin, Fiona Limanaqi, Stefano Gambardella, Alessandro Frati and Francesco Fornai
Int. J. Mol. Sci. 2018, 19(9), 2756; https://doi.org/10.3390/ijms19092756 - 13 Sep 2018
Cited by 29 | Viewed by 4102
Abstract
Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the [...] Read more.
Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the mitochondria and/or proteins are damaged by toxic stimuli. In the present review, we discuss to that extent the recruitment of autophagy is beneficial in counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be detrimental for cell survival. While analyzing these opposite effects, it turns out that the autophagy activity is likely not to be simply good or bad for cell survival, but its role varies depending on the timing and amount of autophagy activation. This calls for the need for an appropriate autophagy tuning to guarantee a beneficial effect on cell survival. Therefore, the present article draws a theoretical pattern of autophagy activation, which is hypothesized to define the appropriate timing and intensity, which should mirrors the duration and severity of brain hypoperfusion. The need for a fine tuning of the autophagy activation may explain why confounding outcomes occur when autophagy is studied using a rather simplistic approach. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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31 pages, 1845 KiB  
Review
The Impact of Aging on Cardio and Cerebrovascular Diseases
by Carmine Izzo, Albino Carrizzo, Antonia Alfano, Nicola Virtuoso, Mario Capunzo, Mariaconsiglia Calabrese, Eros De Simone, Sebastiano Sciarretta, Giacomo Frati, Marco Oliveti, Antonio Damato, Mariateresa Ambrosio, Francesco De Caro, Paolo Remondelli and Carmine Vecchione
Int. J. Mol. Sci. 2018, 19(2), 481; https://doi.org/10.3390/ijms19020481 - 06 Feb 2018
Cited by 63 | Viewed by 10109
Abstract
A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to [...] Read more.
A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand. Full article
(This article belongs to the Special Issue The Impact of Aging on Cardio and Cerebrovascular Diseases)
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