Publications by authors named "Jason D Roh"
Article Synopsis
- Cardiac signaling pathways that respond to exercise can help protect the heart from stress and may offer new treatment options for heart conditions.
- Researchers explored the potential of delivering the CITED4 gene through intravenous AAV9 injections to improve heart recovery from ischemia/reperfusion injury (IRI).
- The study found that CITED4 gene transfer significantly increased CITED4 levels, reduced heart damage, and improved heart function, indicating that this therapy could be a viable method to support heart recovery after ischemic events.
Article Synopsis
- Exercise training enhances heart function and helps protect it from age-related decline and injuries.
- Recent research emphasizes not just the role of cardiomyocytes (heart muscle cells) but also the significant contributions from other cells and systems beyond the heart.
- The review covers various mediators of exercise benefits, including factors related to heart cells and broader influences like metabolism, inflammation, the microbiome, and aging, detailing the molecular mechanisms involved.
Article Synopsis
- Peripartum cardiomyopathy (PPCM) is a pregnancy-related heart failure linked with preeclampsia, and they may share a common biological cause triggered by factors in late pregnancy.
- Researchers found that the senescence-associated secretory phenotype (SASP), indicating cellular aging, is significantly activated in women with PPCM or preeclampsia, particularly noting activin A's role in heart dysfunction severity.
- In studies involving mice, blocking activin A signaling improved heart function postpartum, and using the senolytic compound fisetin during late pregnancy helped enhance cardiac performance, highlighting the connection between aging cells and heart issues during pregnancy.
Article Synopsis
- Preeclampsia is a pregnancy-related condition characterized by high blood pressure and a disruption in the balance of certain proteins, potentially leading to cardiovascular risks due to microvascular dysfunction.
- Researchers compared cardiac function in women with severe preeclampsia to those with normal pregnancies and nonpostpartum controls using advanced imaging techniques to assess myocardial flow and resistance.
- Results indicated that women who had preeclampsia showed significantly decreased blood flow and increased vascular resistance, highlighting reduced coronary microvascular function soon after delivery, which could have long-term health implications.
Article Synopsis
- Preeclampsia is a pregnancy-related condition characterized by high blood pressure and microvascular dysfunction, potentially increasing cardiovascular risks post-pregnancy.
- A study compared women with severe preeclampsia to those with normal pregnancies and non-postpartum controls using cardiac imaging to assess heart function and blood flow.
- Results showed that women who experienced preeclampsia had significantly reduced heart function and increased vascular resistance, indicating potential long-term cardiovascular issues, warranting further investigation for preventive measures.
Article Synopsis
- Hypertensive disorders of pregnancy (HDPs), such as gestational hypertension and preeclampsia, significantly increase risks of maternal health issues and long-term cardiovascular disease across the globe.
- The study aimed to link specific proteins in the blood to HDPs using genetic data, employing two-sample mendelian randomization for analysis.
- Findings involved a broad dataset, including over 393,000 women for gestational hypertension and nearly 607,000 for preeclampsia, uncovering associations between 90 candidate cardiovascular-related proteins and these hypertensive disorders.
Article Synopsis
- The research investigates the potential of exercise to promote the generation of new heart cells (cardiomyocytes) in aged mice, given that the heart’s ability to produce these cells diminishes with age, contributing to heart failure.
- Aged mice underwent an 8-week voluntary running program, and their cardiomyocyte production was assessed and compared to age-matched sedentary mice using advanced imaging techniques.
- Results showed that exercised aged mice had a significantly higher rate of new cardiomyocyte formation than their sedentary counterparts, suggesting that exercise may enhance cardiac regeneration even in older hearts.
Article Synopsis
- Acute and chronic animal models of exercise are used in research to examine how genetic or pharmacological changes affect cardiovascular responses and functions during exercise.
- Acute exercise testing helps identify cardiovascular issues not visible at rest, while chronic models assess long-term training effects and discover therapeutic pathways linked to exercise benefits.
- The review also covers methods for evaluating rodent cardiovascular function during exercise and introduces feeding in the Burmese python as a potential model for studying exercise-related physiological adaptations.
Article Synopsis
- * Highlighted the roles of specific proteins, FSTL3 and ADAMTS13, in causing myocardial stress and microvascular issues in COVID-19.
- * Validated findings through a larger patient cohort and an animal model, offering potential new targets for therapy in cardiovascular issues related to COVID-19.
Article Synopsis
- Arterial stiffness is identified as a risk factor for cardiovascular diseases, particularly heart failure with preserved ejection fraction (HFpEF), and circulating levels of inactive matrix Gla protein (ucMGP) are linked to these health issues.
- In a study analyzing data from the Framingham Heart Study, higher levels of ucMGP were associated with increased arterial stiffness and were predictive of future heart failure and rising blood pressure.
- Experimental studies in mice also showed that older Mgp mice exhibited increased arterial stiffness, supporting the notion that targeting MGP could be a potential therapeutic strategy for addressing HFpEF.
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown.
View Article and Find Full Text PDFArticle Synopsis
- Aging causes the heart to weaken, making older adults more prone to heart failure, necessitating interventions to address this decline.
- Our knowledge about how aging affects the heart is still growing, but recent research has identified important mechanisms and protective strategies, particularly through exercise.
- This review emphasizes the latest discoveries in heart failure related to aging and suggests that exercise could be a key area for finding new treatments.
Article Synopsis
- Activin type II receptor (ActRII) ligands play a role in muscle wasting associated with aging and diseases, but their impact on heart health is not well understood.
- This study used circulating follistatin-like 3 (FSTL3) as a marker for ActRII activity, revealing that higher FSTL3 levels correlated with aging, frailty, and heart failure (HF) severity in humans.
- In animal models, increased levels of activin A led to worsened heart function due to enhanced ActRII signaling, while blocking this signaling pathway improved cardiac health, suggesting that targeting this pathway could be a potential treatment for heart failure.
Article Synopsis
- Direct invasion of the heart from the pericardium can lead to cardiac tuberculosis.
- Granulomas caused by tuberculosis can narrow blood vessels, affecting blood flow.
- These granulomas can shrink completely with the right tuberculosis treatment, and a transthoracic echocardiogram (TTE) is important for spotting complications and tracking how well the treatment works.
Article Synopsis
- Cardiac macrophages play key roles in heart health and disease, particularly in diastolic dysfunction, which is linked to aging and heart failure.
- Research shows that these macrophages increase in number with conditions like hypertension and old age, and this expansion is driven by monocyte recruitment from the bone marrow and spleen.
- In cases of diastolic dysfunction, cardiac macrophages produce IL-10, which contributes to collagen buildup and stiffness in heart tissue, and targeting these macrophages could offer new strategies for treating cardiac fibrosis.
Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi-Goutières syndrome and STING-associated vasculopathy of infancy (SAVI). Myocardial infarction (MI) elicits inflammation, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production.
View Article and Find Full Text PDFWe developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin.
View Article and Find Full Text PDFBiodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds.
View Article and Find Full Text PDFBackground: Use of prosthetic vascular grafts in pediatric vascular surgical applications is limited because of risk of infection, poor durability, potential for thromboembolic complications, and lack of growth potential. Construction of an autologous neovessel using tissue engineering technology offers the potential to create an improved vascular conduit for use in pediatric vascular applications.
Methods: Tissue-engineered vascular grafts were assembled from biodegradable tubular scaffolds fabricated from poly-L-lactic acid mesh coated with epsilon-caprolactone and L-lactide copolymer.
Introduction: The development of a living, autologous vascular graft with the ability to grow holds great promise for advancing the field of pediatric cardiothoracic surgery.
Objective: To evaluate the growth potential of a tissue-engineered vascular graft (TEVG) in a juvenile animal model.
Methods: Polyglycolic acid nonwoven mesh tubes (3-cm length, 1.
Hypothesis: The immunodeficient (severe combined immunodeficiency beige [SCID/bg]) mouse model provides a useful model for investigating vascular neotissue formation in human tissue-engineered arterial conduits (TEAC).
Design: Human aortic smooth muscle cells and endothelial cells were statically seeded on porous biodegradable polymeric scaffolds for vascular tissue engineering. These 2-cell tissue-engineered vascular conduits were implanted into immunodeficient female mice as aortic interposition grafts.
The development of neotissue in tissue engineered vascular grafts remains poorly understood. Advances in mouse genetic models have been highly informative in the study of vascular biology, but have been inaccessible to vascular tissue engineers due to technical limitations on the use of mouse recipients. To this end, we have developed a method for constructing sub-1mm internal diameter (ID) biodegradable scaffolds utilizing a dual cylinder chamber molding system and a hybrid polyester sealant scaled for use in a mouse model.
View Article and Find Full Text PDFBone marrow stromal cells (MSCs) are a promising cell source for a variety of tissue engineering applications, given their ready availability and ability to differentiate into multiple cell lineages. MSCs have been successfully used to create neotissue for cardiovascular, urological, and orthopedic reconstructive surgical procedures in preclinical studies. The ability to optimize seeding techniques of MSCs onto tissue engineering scaffolds and the ability to control neotissue formation in vitro will be important for the rational design of future tissue engineering applications using MSCs.
View Article and Find Full Text PDFBackground: Currently available vascular grafts for pediatric cardiovascular operations are limited by their inability to grow. Tissue-engineering techniques can be used to create vascular grafts with the potential for repair, remodeling, and growth. This study demonstrates the feasibility of constructing an autologous tissue-engineered venous conduit from bone marrow-derived vascular cells (BMVCs) in the ovine animal model.
View Article and Find Full Text PDF