Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.
{"title":"Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy","authors":"R. Madonna","doi":"10.20517/jca.2021.34","DOIUrl":"https://doi.org/10.20517/jca.2021.34","url":null,"abstract":"Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dr. McKenna and colleagues interpret the histology figure to diagnose cor adiposum in family member III-4 who died suddenly and was found to have extensive fibro-adiposis of the right ventricle[1]. The authors apparently made their diagnosis indicating that fibrosis is necessary for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). We had described the histological data as “fibro-fatty infiltration of the right ventricle, encompassing 50% to 80% of the right ventricular wall thickness”[1]. However, we had not included specific staining for myocardial fibrosis. We provide Masson trichrome-stained myocardial sections, which show unequivocal evidence of myocardial fibrosis along with the excess adipocytes [Figure 1]. We also note that individual III-4 had pathogenic and likely pathogenic variants (PVs/LPVs) in the PKP2 and DSP genes, which are well-established causes of ARVC. Furthermore, cor adiposum does not exclusively and extensively involve the right ventricle, as observed in individual III-4, without involving the left ventricle. Thus, the data firmly refutes the diagnosis of cor adiposum and confirms the diagnosis of the classic ARVC.
{"title":"Oligogenic cardiomyopathy.","authors":"Ali J Marian","doi":"10.20517/jca.2021.27","DOIUrl":"https://doi.org/10.20517/jca.2021.27","url":null,"abstract":"Dr. McKenna and colleagues interpret the histology figure to diagnose cor adiposum in family member III-4 who died suddenly and was found to have extensive fibro-adiposis of the right ventricle[1]. The authors apparently made their diagnosis indicating that fibrosis is necessary for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). We had described the histological data as “fibro-fatty infiltration of the right ventricle, encompassing 50% to 80% of the right ventricular wall thickness”[1]. However, we had not included specific staining for myocardial fibrosis. We provide Masson trichrome-stained myocardial sections, which show unequivocal evidence of myocardial fibrosis along with the excess adipocytes [Figure 1]. We also note that individual III-4 had pathogenic and likely pathogenic variants (PVs/LPVs) in the PKP2 and DSP genes, which are well-established causes of ARVC. Furthermore, cor adiposum does not exclusively and extensively involve the right ventricle, as observed in individual III-4, without involving the left ventricle. Thus, the data firmly refutes the diagnosis of cor adiposum and confirms the diagnosis of the classic ARVC.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39942023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chandrika Canugovi, M. Stevenson, Aleksandr E. Vendrov, A. Lozhkin, S. Britton, L. Koch, M. Runge, N. Madamanchi
Introduction: Low aerobic exercise capacity is an independent risk factor for cardiovascular disease (CVD) and a predictor of premature death. In combination with aging, low aerobic capacity lowers the threshold for CVD. Aim: Since low aerobic capacity and aging have been linked to mitochondrial oxidative stress and dysfunction, we investigated whether aged Low-Capacity Runner (LCR) rats (27 months) had vascular dysfunction compared to High-Capacity Runner (HCR) rats. Methods and Results: A significant decrease in aortic eNOS levels and vasodilation as well as an increase in aortic collagen and stiffness were observed in aged LCR rats compared to age and sex-matched HCR rats. There was a correlation between age-related vascular dysfunction and increased levels of ROS and DNA damage in aortas of LCR rats. Moreover, mitochondrial oxygen consumption, membrane potential, ATP levels, and mitophagy were lower in VSMCs of aged LCR rats. VSMCs from older LCR rats showed AIM2 inflammasome activation. VSMCs of young (4 months old) LCR rats treated with purified mitochondrial damage-associated molecular patterns (DAMP) recapitulated an inflammasome activation phenotype similar to that seen in aged rat VSMCs. Rapamycin, a potent immunosuppressant, induced mitophagy, stimulated electron transport chain activity, reduced inflammasome activity, mitochondrial ROS and DAMP levels in VSMCs from aged LCR rats. MitoTEMPO, a mitochondrial ROS scavenger, was similarly effective on VSMCs from aged rats. Conclusion: The findings suggest that impaired mitophagy and inflammasome activation in the vasculature under conditions of low aerobic exercise capacity during aging results in arterial dysfunction and aortic stiffness. In older adults with reduced aerobic capacity, mitochondrial antioxidants, mitophagy induction, and inflammasome inhibition may be effective therapeutic strategies for enhancing vascular health.
{"title":"Mitochondrial DAMPs-dependent inflammasome activation during aging induces vascular smooth muscle cell dysfunction and aortic stiffness in low aerobic capacity rats","authors":"Chandrika Canugovi, M. Stevenson, Aleksandr E. Vendrov, A. Lozhkin, S. Britton, L. Koch, M. Runge, N. Madamanchi","doi":"10.20517/jca.2022.35","DOIUrl":"https://doi.org/10.20517/jca.2022.35","url":null,"abstract":"Introduction: Low aerobic exercise capacity is an independent risk factor for cardiovascular disease (CVD) and a predictor of premature death. In combination with aging, low aerobic capacity lowers the threshold for CVD. Aim: Since low aerobic capacity and aging have been linked to mitochondrial oxidative stress and dysfunction, we investigated whether aged Low-Capacity Runner (LCR) rats (27 months) had vascular dysfunction compared to High-Capacity Runner (HCR) rats. Methods and Results: A significant decrease in aortic eNOS levels and vasodilation as well as an increase in aortic collagen and stiffness were observed in aged LCR rats compared to age and sex-matched HCR rats. There was a correlation between age-related vascular dysfunction and increased levels of ROS and DNA damage in aortas of LCR rats. Moreover, mitochondrial oxygen consumption, membrane potential, ATP levels, and mitophagy were lower in VSMCs of aged LCR rats. VSMCs from older LCR rats showed AIM2 inflammasome activation. VSMCs of young (4 months old) LCR rats treated with purified mitochondrial damage-associated molecular patterns (DAMP) recapitulated an inflammasome activation phenotype similar to that seen in aged rat VSMCs. Rapamycin, a potent immunosuppressant, induced mitophagy, stimulated electron transport chain activity, reduced inflammasome activity, mitochondrial ROS and DAMP levels in VSMCs from aged LCR rats. MitoTEMPO, a mitochondrial ROS scavenger, was similarly effective on VSMCs from aged rats. Conclusion: The findings suggest that impaired mitophagy and inflammasome activation in the vasculature under conditions of low aerobic exercise capacity during aging results in arterial dysfunction and aortic stiffness. In older adults with reduced aerobic capacity, mitochondrial antioxidants, mitophagy induction, and inflammasome inhibition may be effective therapeutic strategies for enhancing vascular health.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-08-05DOI: 10.20517/jca.2022.33
Jamie Francisco, Dominic P Del Re
Cellular senescence is a concerted process that involves a stable cell cycle arrest despite continued metabolic activity, and the development of a pro-inflammatory response known as the senescence-associated secretory phenotype (SASP) [1] . Aging and senescence have long been associated, and studies employing senolytic approaches, i.e., the targeted removal of senescent cells, have demonstrated a causal role for their actions in aging-related phenotypes in various tissues [2] . Presumably, due to the nature of SASP, this process is largely non-cell autonomous and involves paracrine effects on neighboring cells to promote organ dysfunction. senolytic approaches aging-related tissue linked physiological aging and cellular to a decline in mechanotransduction mediated by decreased YAP/TAZ activity findings
{"title":"YAP/TAZ dull the STING of aging.","authors":"Jamie Francisco, Dominic P Del Re","doi":"10.20517/jca.2022.33","DOIUrl":"https://doi.org/10.20517/jca.2022.33","url":null,"abstract":"Cellular senescence is a concerted process that involves a stable cell cycle arrest despite continued metabolic activity, and the development of a pro-inflammatory response known as the senescence-associated secretory phenotype (SASP) [1] . Aging and senescence have long been associated, and studies employing senolytic approaches, i.e., the targeted removal of senescent cells, have demonstrated a causal role for their actions in aging-related phenotypes in various tissues [2] . Presumably, due to the nature of SASP, this process is largely non-cell autonomous and involves paracrine effects on neighboring cells to promote organ dysfunction. senolytic approaches aging-related tissue linked physiological aging and cellular to a decline in mechanotransduction mediated by decreased YAP/TAZ activity findings","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40682906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-01-05DOI: 10.20517/jca.2021.30
Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian
The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed by a reverse transcription-polymerase chain reaction in independent samples, correlated with changes in the RNA-sequencing data. The differentially expressed genes were modestly enriched for genes involved in the interferon response and the tumor protein 53 (TP53) pathways. The changes in gene expression were relatively small and mostly transient and had no discernible effects on cardiac function, myocardial fibrosis, and apoptosis or induction of double-stranded DNA breaks. Thus, TAM-inducible activation of MCM alters cardiac myocytes gene expression, provoking modest and transient interferon and DNA damage responses without exerting other discernible phenotypic effects. Thus, the effects of TAM-MCM on gene expression should be considered in discerning the bona fide changes that result from the targeting of the gene of interest.
{"title":"Effects of tamoxifen inducible MerCreMer on gene expression in cardiac myocytes in mice.","authors":"Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian","doi":"10.20517/jca.2021.30","DOIUrl":"https://doi.org/10.20517/jca.2021.30","url":null,"abstract":"<p><p>The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (<i>Myh6-Mcm</i>) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed by a reverse transcription-polymerase chain reaction in independent samples, correlated with changes in the RNA-sequencing data. The differentially expressed genes were modestly enriched for genes involved in the interferon response and the tumor protein 53 (TP53) pathways. The changes in gene expression were relatively small and mostly transient and had no discernible effects on cardiac function, myocardial fibrosis, and apoptosis or induction of double-stranded DNA breaks. Thus, TAM-inducible activation of MCM alters cardiac myocytes gene expression, provoking modest and transient interferon and DNA damage responses without exerting other discernible phenotypic effects. Thus, the effects of TAM-MCM on gene expression should be considered in discerning the bona fide changes that result from the targeting of the gene of interest.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39949695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-07-20DOI: 10.20517/jca.2022.30
Dan Tong
Graphical Abstract
{"title":"SGLT2 inhibitors in patients with HFpEF: how old is too old?","authors":"Dan Tong","doi":"10.20517/jca.2022.30","DOIUrl":"https://doi.org/10.20517/jca.2022.30","url":null,"abstract":"Graphical Abstract","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40590477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"To Live in Your Growth Zone, You Need to Leave Your Comfort Zone","authors":"L. Rouhi","doi":"10.20517/jca.2022.22","DOIUrl":"https://doi.org/10.20517/jca.2022.22","url":null,"abstract":"","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linjuan Guo, Yuhao Su, Chen Chen, Qiongqiong Zhou, Yang Shen, Zhenhong Jiang, Xia Yan, Xiaoqing Li, Wen Zhuo, Xiaogang Peng, R. Wan, K. Hong
Introduction: The TNNI3 gene encodes the protein of cardiac troponin I (cTnI), which is an inhibitory subunit of sarcomeres. Mutations in this gene account for 3% of hypertrophic cardiomyopathy (HCM) and the molecular mechanism is complex. Recently, lipid metabolism has been revealed to be involved in HCM. Aim: The purpose of this work is to identify whether the pathological mechanism of the hotspot mutation TNNI3 p.R186Q in HCM is related to abnormal lipid metabolism. Methods and Results: A knock-in (KI) mouse model carrying the Tnni3 p.R186Q homozygous mutation (Tnni3R186Q/R186Q) was novelty generated by CRISPR/Cas9 technology and successfully constructed a typical phenotype of cardiac-myopathy. Likewise, neonatal rat cardiomyocytes (NRCMs) transfected with a mutant plasmid with the TNNI3 p.R186Q mutation showed the same phenomenon. In-depth experiments on related functions and molecular mechanisms were conducted, and Tnni3R186Q/R186Q mice exhibited abnormal fatty acid metabolism, which was induced by the activation of epidermal growth factor receptor (EGFR)-dependent high expression of fatty acid synthase (FASN) in vivo and in vitro. Specifically, the direct binding of EGFR and cTnI was destroyed by TNNI3 p.R186Q mutation, as observed through bioinformatics, Co-IP and GST-pull down analysis. Conclusion: In the present study, we successfully engineered Tnni3R186Q/R186Q mice with the typical phenotype of myocardial hypertrophy. We demonstrated that the TNNI3 p.R186Q mutation could induce HCM by the dissociation of EGFR and cTnI, which further led to EGFR-dependent increased expression of FASN and abnormal lipid metabolism.
{"title":"The TNNI3 p.R186Q mutation is responsible for hypertrophic cardiomyopathy via promoting FASN-stimulated abnormal fatty acid metabolism","authors":"Linjuan Guo, Yuhao Su, Chen Chen, Qiongqiong Zhou, Yang Shen, Zhenhong Jiang, Xia Yan, Xiaoqing Li, Wen Zhuo, Xiaogang Peng, R. Wan, K. Hong","doi":"10.20517/jca.2022.29","DOIUrl":"https://doi.org/10.20517/jca.2022.29","url":null,"abstract":"Introduction: The TNNI3 gene encodes the protein of cardiac troponin I (cTnI), which is an inhibitory subunit of sarcomeres. Mutations in this gene account for 3% of hypertrophic cardiomyopathy (HCM) and the molecular mechanism is complex. Recently, lipid metabolism has been revealed to be involved in HCM. Aim: The purpose of this work is to identify whether the pathological mechanism of the hotspot mutation TNNI3 p.R186Q in HCM is related to abnormal lipid metabolism. Methods and Results: A knock-in (KI) mouse model carrying the Tnni3 p.R186Q homozygous mutation (Tnni3R186Q/R186Q) was novelty generated by CRISPR/Cas9 technology and successfully constructed a typical phenotype of cardiac-myopathy. Likewise, neonatal rat cardiomyocytes (NRCMs) transfected with a mutant plasmid with the TNNI3 p.R186Q mutation showed the same phenomenon. In-depth experiments on related functions and molecular mechanisms were conducted, and Tnni3R186Q/R186Q mice exhibited abnormal fatty acid metabolism, which was induced by the activation of epidermal growth factor receptor (EGFR)-dependent high expression of fatty acid synthase (FASN) in vivo and in vitro. Specifically, the direct binding of EGFR and cTnI was destroyed by TNNI3 p.R186Q mutation, as observed through bioinformatics, Co-IP and GST-pull down analysis. Conclusion: In the present study, we successfully engineered Tnni3R186Q/R186Q mice with the typical phenotype of myocardial hypertrophy. We demonstrated that the TNNI3 p.R186Q mutation could induce HCM by the dissociation of EGFR and cTnI, which further led to EGFR-dependent increased expression of FASN and abnormal lipid metabolism.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rurik et al. [1] published in Science provide results from an elegant proof-of-concept study that modified messenger RNA (mRNA) encapsulated in targeted lipid nanoparticles (LNPs) can be delivered intravenously to produce functional engineered T cells in vivo . Specifically, they generated transient anti-fibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified mRNA in CD5 T cell-targeted LNPs.
{"title":"The use of targeted LNP/mRNA technology to generate functional, transient CAR T cells and treat cardiac injury in vivo","authors":"G. Ellison‐Hughes","doi":"10.20517/jca.2022.05","DOIUrl":"https://doi.org/10.20517/jca.2022.05","url":null,"abstract":"Rurik et al. [1] published in Science provide results from an elegant proof-of-concept study that modified messenger RNA (mRNA) encapsulated in targeted lipid nanoparticles (LNPs) can be delivered intravenously to produce functional engineered T cells in vivo . Specifically, they generated transient anti-fibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified mRNA in CD5 T cell-targeted LNPs.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67657538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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