Abstract P440: Cardiac Tissue Chip Model Provides A Platform For Studying Age-related Cardiovascular Complications By Recapitulating Important Hallmarks Of Senescence And Myocardial Ischemia

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Sachin Budhathoki ◽  
Caleb Graham ◽  
Palaniappan Sethu ◽  
Ramaswamy Kannappan
Keyword(s):  
Cardiovascular Disease ◽  
Myocardial Ischemia ◽  
Cardiac Tissue ◽  
The Elderly ◽  
Cardiovascular Complications ◽  
Cell Alignment ◽  
Doxorubicin Treatment ◽  
Tissue Model ◽  
Age Related ◽  
Peptide Expression

Introduction: With the rise in the elderly population, there has been an exponential growth in cardiovascular diseases and age-related complications. This necessitates a platform for studying cardiovascular disease in the context of aging. Hypothesis: An engineered cardiac tissue model that can recapitulate critical aspects of aging can be used to study age-related diseases of the cardiovascular system. Methods: Senescence was induced in rat cardiomyoblasts using an acute low-dose doxorubicin treatment. The presence of important senescent markers in the cells like enlarged and flattened nuclei, increased ROS activity, elevated p53 production, DNA damage response foci, and increased expression of cell cycle inhibitor p16 INK4a was evaluated. These senescent cells were then used to engineer cardiac tissue, which was subjected to hemodynamic stresses associated with the pressure-volume changes in the heart. Myocardial ischemia was imposed in the aging cardiac tissue model using hypoxic treatment. Results: Under normal hemodynamic loading, the engineered cardiac tissue retained its cardiac cell characteristics and showed cell alignment along with age-related changes in structure and gene expression. The myocardial ischemic model of the tissue revealed major pathological hallmarks of the disease like increased cell death and natriuretic peptide expression. Conclusion: Our model and methodology provide an effective platform for studying the cardiovascular disease pathologies associated with aging and screening drugs against age-related complications.

Engineered Aging Cardiac Tissue Chip Model for Studying Cardiovascular Disease

2021 ◽  
pp. 1-12
Author(s):  
Sachin Budhathoki ◽  
Caleb Graham ◽  
Palaniappan Sethu ◽  
Ramaswamy Kannappan
Keyword(s):  
Cardiovascular Disease ◽  
Low Dose ◽  
Cardiac Tissue ◽  
Disease Modeling ◽  
Cardiovascular Complications ◽  
Cardiac Cell ◽  
Cell Alignment ◽  
Doxorubicin Treatment ◽  
Age Related ◽  
Tissue Chip

Due to the rapidly growing number of older people worldwide and the concomitant increase in cardiovascular complications, there is an urgent need for age-related cardiac disease modeling and drug screening platforms. In the present study, we developed a cardiac tissue chip model that incorporates hemodynamic loading and mimics essential aspects of the infarcted aging heart. We induced cellular senescence in H9c2 myoblasts using low-dose doxorubicin treatment. These senescent cells were then used to engineer cardiac tissue fibers, which were subjected to hemodynamic stresses associated with pressure-volume changes in the heart. Myocardial ischemia was modeled in the engineered cardiac tissue via hypoxic treatment. Our results clearly show that acute low-dose doxorubicin treatment-induced senescence, as evidenced by morphological and molecular markers, including enlarged and flattened nuclei, DNA damage response foci, and increased expression of cell cycle inhibitor p16<sup>INK4a</sup>, p53, and ROS. Under normal hemodynamic load, the engineered cardiac tissues demonstrated cell alignment and retained cardiac cell characteristics. Our senescent cardiac tissue model of hypoxia-induced myocardial infarction recapitulated the pathological disease hallmarks such as increased cell death and upregulated expression of ANP and BNP. In conclusion, the described methodology provides a novel approach to generate stress-induced aging cardiac cell phenotypes and engineer cardiac tissue chip models to study the cardiovascular disease pathologies associated with aging.

Abstract 15948: Inhibition of NF-kB Signaling Attenuates Age-related Aggravation of Myocardial Ischemia/Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Guangming Cheng ◽  
Sheng Ye ◽  
Magdy Girgis ◽  
Lin Zhao ◽  
Xing Chen ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Elderly ◽  
Age Related ◽  
Redox Responsive ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Introduction: Emerging evidence indicates that myocardial ischemia/reperfusion (I/R) injury is more severe in aged hearts. Although nuclear factor-kappaB (NF-kB) activity increases with aging, whether this redox-responsive transcription factor plays any role in age-related worsening of I/R injury remains unknown. Hypothesis: We hypothesized that activation of myocardial NF-kB exerts deleterious effects during I/R injury in young as well as aged hearts; and that NF-kB signaling contributes to age-related worsening of myocardial I/R injury. Methods: We used transgenic mice overexpressing a mutant IkBa that prevents NF-kB activation only in the heart. Age-matched young (10-week-old) and aged (86-week-old) male non-transgenic littermates (NTg) and IkBa transgenic (Tg) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Following sacrifice, infarct size was measured and molecular assays were performed. Results: The infarct size was significantly smaller in young Tg mice compared with young NTg mice (Fig), indicating a deleterious role of NF-kB signaling during myocardial I/R injury even in the young. The infarct size in aged NTg hearts was greater compared with young NTg hearts, consistent with an age-related worsening of I/R injury effects. However, infarct size in aged Tg hearts was significantly smaller than aged NTg hearts, and similar to young Tg hearts, indicating that NF-kB signaling contributes toward age-related aggravation of I/R injury. Interestingly, the levels of molecular markers of senescence, such as p16, were lower in aged Tg hearts (Fig), indicating a deleterious role of NF-kB in cardiac aging and susceptibility to I/R injury. Conclusions: We conclude that inhibition of cardiac NF-kB signaling protects against age-related aggravation of acute myocardial I/R injury. These findings suggest that modulation of NF-kB signaling may be potentially used to achieve therapeutic cardioprotection in the elderly.

scholarly journals Findings on the relationship between cardiovascular disease and coronavirus disease 2019: a systematic review

2020 ◽  
Author(s):  
Yuri Henrique da Silva1 ◽  
José Gildo de Moura Monteiro Júnior ◽  
Rosângela Ferreira Frade de Araújo
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Cardiac Injury ◽  
The Elderly ◽  
Cardiovascular Complications ◽  
Cardiac Insufficiency ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Cardiovascular Comorbidities ◽  
Number Of Patients

Abstract Coronavirus disease 2019 (COVID-19) presents as the main cause of death, respiratory and heart failures, especially in the elderly, immunosuppressed, and those with cardiovascular comorbidities. Therefore, a better understanding of these findings is needed. A systematic review was carried out looking for articles published between December 2019 and May 2020 on the MEDLINE / PubMed search platform using the following descriptors: ((((((((("cardiovascular disease") OR ("acute myocardial infarction")) OR ("coronary artery disease")) OR ("acute coronary syndrome")) OR ("atherosclerosis")) OR ("cardiac insufficiency")) OR ("pericarditis")) OR ("myocarditis")) AND ("COVID-19")) OR ("SARS-CoV-2")and considering inclusion and exclusion criteria.40% of patients infected with SARS-CoV-2 had hypertension or other cardiovascular comorbidities, while 27% presented cardiovascular complications, mainly acute cardiac injury, arrhythmia and heart failure. The hypotheses of involvement of an intense inflammatory response, decreased immunity and greater expression of ACE2 in the heart, associated with more severe heart conditions, were discussed in this study. The increase in cardiac and inflammatory markers was associated with worse clinical outcomes and risk of death, confirming the need to evaluate them since admission to the hospital. The 10 articles analyzed presented as a limitation the small number of patients inserted, to the detriment of the pandemic state. We warned about the need for better clinical management of patients with cardiovascular comorbidities, and the importance of including this group among the first to be immunized, aiming at reducing the number of fatal cases due to infection. Studies with greater coverage are needed for a better comprehension of the topics discussed here.

scholarly journals Mechanisms of Myocardial Injury in Coronavirus Disease 2019

2020 ◽  
Vol 6 ◽  
Author(s):  
Aniket S Rali ◽  
Sagar Ranka ◽  
Zubair Shah ◽  
Andrew J Sauer
Keyword(s):  
Cardiovascular Disease ◽  
Respiratory Failure ◽  
Myocardial Injury ◽  
Myocardial Dysfunction ◽  
The Elderly ◽  
Cardiovascular Complications ◽  
Myocardial Inflammation

Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.

Special situations in the elderly: sport, physical activity, and travel

ESC CardioMed ◽  
2018 ◽  
pp. 2976-2980
Author(s):  
Joanna Kostka ◽  
Małgorzata Koziarska-Rościszewska ◽  
Tomasz Kostka
Keyword(s):  
Physical Activity ◽  
Chronic Diseases ◽  
Malaria Prevention ◽  
The Elderly ◽  
Training Programme ◽  
Cardiovascular Complications ◽  
Physically Active ◽  
Older Athletes ◽  
Age Related ◽  
Cardiovascular Evaluation

The number of physically active and travelling older people is gradually increasing. Regular physical activity can bring significant health benefits to people of all ages. On the other hand, due to concomitant chronic diseases and age-related changes, older athletes are at higher risk of both acute adverse events and overuse injuries. Therefore, general medical and cardiovascular evaluation is recommended before initiation of a training programme. Similarly, it is necessary to perform a medical assessment of older subjects concerning fitness for travel and possible medical consequences. A pre-travel visit should allow individual physical and mental limitations for travel to be discussed and provide a patient with necessary prophylaxis, such as vaccinations or malaria prevention. Special problems in older athletes and travellers with chronic diseases should be taken into consideration (e.g. the risk of venous thromboembolism during prolonged exercise or travel in hot environment). Older adults with concomitant co-morbidities constitute a growing percentage of subjects participating in sports or undertaking travel. Although they are at higher risk of cardiovascular complications, a general recommendation to ‘avoid inactivity’ may nowadays be put forward.

Special situations in the elderly: sport, physical activity, and travel

ESC CardioMed ◽  
2018 ◽  
pp. 2976-2980
Author(s):  
Joanna Kostka ◽  
Małgorzata Koziarska-Rościszewska ◽  
Tomasz Kostka
Keyword(s):  
Physical Activity ◽  
Malaria Prevention ◽  
The Elderly ◽  
Training Programme ◽  
Cardiovascular Complications ◽  
Physically Active ◽  
Hot Environment ◽  
Older Athletes ◽  
Age Related ◽  
Cardiovascular Evaluation

The number of physically active and travelling older people is gradually increasing. Regular physical activity can bring significant health benefits to people of all ages. On the other hand, due to concomitant chronic disease and age-related changes, older athletes are at higher risk of both acute adverse events and overuse injuries. Therefore, general medical and cardiovascular evaluation is recommended before initiation of a training programme. Similarly, it is necessary to perform a medical assessment of older subjects concerning fitness for travel and possible medical consequences. A pre-travel visit should allow individual physical and mental limitations for travel to be discussed and provide a patient with necessary prophylaxis, such as vaccinations or malaria prevention. Special problems in older athletes and travellers with chronic diseases should be taken into consideration (e.g. the risk of venous thromboembolism during prolonged exercise or travel in hot environment). Older adults with concomitant co-morbidities constitute a growing percentage of subjects participating in sports or undertaking travel. Although they are at higher risk of cardiovascular complications, a general recommendation to ‘avoid inactivity’ may be nowadays be put forward.

scholarly journals Cardiac rehabilitation protocols in the elderly

2020 ◽  
Vol 90 (4) ◽  
Author(s):  
Maria Vittoria Silverii ◽  
Alessandra Pratesi ◽  
Giulia Lucarelli ◽  
Francesco Fattirolli
Keyword(s):  
Cardiovascular Disease ◽  
Cardiac Rehabilitation ◽  
The Elderly ◽  
Great Effort ◽  
Very Old ◽  
Multidisciplinary Program ◽  
Frail Patients ◽  
Age Related ◽  
Multidimensional Evaluation ◽  
Rehabilitation Protocols

Cardiac rehabilitation (CR) is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. Cardiovascular disease is prevalent in older adults and is the leading cause of death and major disability in adults ≥75 years of age. The mean age of patients eligible for CR is increasing, with greater complexity and specific geriatric features, such as multimorbidity, frailty, and disability. In this population, CR interventions should be aimed to prevent disability and preserve the residual functional capacity. Every patient should be assessed with a multidimensional evaluation that includes clinical, functional, emotional, cognitive and social domains. Exercise-based CR programs have shown to be effective in improving function and quality of life, by reducing disability and age-related deconditioning and contributing favorably to improved health outcomes in an aged population. Very old and frail patients seem to get an even greater potential benefit, and an early start after an acute event can prevent the post-hospital syndrome. Despite these proven benefits, CR is often underused in this population and a great effort should be done to encourage them to attend these programs. There are just a few studies about CR programs in very old and frail patients, therefore a future goal should be to fill this gap.

scholarly journals Spatiotemporal Changes of Tissue Glycans Depending on Localization in Cardiac Aging

2021 ◽  
Author(s):  
Yoko Itakura ◽  
Yasuko Hasegawa ◽  
Yurika Kikkawa ◽  
Yuina Murakami ◽  
Chiaki Nagai-Okatani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiac Tissue ◽  
Signs And Symptoms ◽  
Healthy Life ◽  
Lectin Staining ◽  
Age Related ◽  
Luminal Side ◽  
Spatiotemporal Changes ◽  
The Difference

Abstract Heart failure is caused by various factors, making its underlying pathogenic mechanisms difficult to identify, and tends to worsen over time. Early diagnosis of cardiovascular disease is the key for treatment to promote healthy life. To detect the structural and functional molecular changes associated with cardiovascular disease, we focused on glycans, which reflect the type and state of cells. We investigated glycan localization in the cardiac tissue of normal mice and their alterations during aging using an evanescent-filed lectin microarray, a technique based on lectin-glycan interaction, and lectin staining. The glycan profiles in the left ventricle showed differences between the luminal side (medial) and the wall side (lateral) region. The former area was characterized by the presence of sialic acid residues.Moreover, age-related changes in glycan profiles were observed earlier in the medial region. The difference in the age-related decrease of a-galactose stained with griffonia simplicifolia lectin-IB4 in different region of the leftventricle suggested spatiotemporal changes in microvessels. The glycan profile, which retains diverse glycan structures, is supported by many cell populations and maintains cardiac function. Glycan localization and changes are expected to be developed as a marker of the signs and symptoms of heart failure in the future.

The Biological Clock and Sleep in the Elderly

2006 ◽  
Vol 19 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Myriam Juda ◽  
Mirjam Münch ◽  
Anna Wirz-Justice ◽  
Martha Merrow ◽  
Till Roenneberg
Keyword(s):  
Circadian Rhythms ◽  
Biological Clock ◽  
The Elderly ◽  
Early Morning ◽  
Behavioral Changes ◽  
Older Age ◽  
Age Related ◽  
Theoretical Considerations ◽  
Sleep Difficulties ◽  
Circadian Biology

Abstract: Among many other changes, older age is characterized by advanced sleep-wake cycles, changes in the amplitude of various circadian rhythms, as well as reduced entrainment to zeitgebers. These features reveal themselves through early morning awakenings, sleep difficulties at night, and a re-emergence of daytime napping. This review summarizes the observations concerning the biological clock and sleep in the elderly and discusses the documented and theoretical considerations behind these age-related behavioral changes, especially with respect to circadian biology.

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