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Mashup Score: 0Interorgan Crosstalk in Heart Failure and Cardiometabolic Diseases: A Compendium | Circulation Research - 7 hour(s) ago
Cardiovascular disease rarely exists in isolation. Heart failure and cardiometabolic disorders are systemic conditions shaped not only by primary cardiac pathophysiology but also by dynamic, bidirectional interactions between the heart and peripheral organs. These interorgan communication pathways—mediated through neural, immune, endocrine, metabolic, and mechanical signals—have emerged as central players in disease progression, multimorbidity, and therapeutic resistance. Yet, our understanding of these
Source: www.ahajournals.orgCategories: General Medicine NewsTweet
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Mashup Score: 21Discover Circ Res May 2025 | AHA Podcasts - 10 hour(s) ago
This month on Episode 72 of Discover CircRes, host Cindy St. Hilaire highlights four articles featured in the April 25th and May 9th issues of Circulation Research. This Episode also includes a discussion with Dr. Sarah Costantino and Dr. Francesco Paneni from University Hospital Zurich about their study, Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF This month on Episode 72 of Discover CircRes, host Cindy St. Hilaire highlights four articles featured in the April 25th and
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
1/5 New @CircRes podcast #DiscoverCircRes https://t.co/qeE1QIIZLv @StHilaireLab chats with @francescopaneni and Sarah Costantino about their study Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF https://t.co/i2w3Lfv1XY @UZH_en https://t.co/fVbzLDKmOA
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Mashup Score: 23The Heart Has Intrinsic Ketogenic Capacity that Mediates NAD+ Therapy in HFpEF | Circulation Research - 3 day(s) ago
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbidity and mortality rates, yet with only a single approved pharmacotherapy: SGLT2i (sodium-glucose co-transporter 2 inhibitor). A prevailing theory for the mechanism underlying SGLT2i is nutrient deprivation signaling, of which ketogenesis is a hallmark. However, it is unclear whether the canonical ketogenic enzyme, HMGCS2 (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2), plays any cardiac role in HFpEF pathogenesis or therapeutic response. METHODS: We used human myocardium, human HFpEF and heart failure with reduced ejection fraction transcardiac blood sampling, an established murine model of HFpEF, ex vivo Langendorff perfusion, stable isotope tracing in isolated cardiomyocytes, targeted metabolomics, proteomics, lipidomics, and a novel cardiomyocyte-specific conditional HMGCS2-deficient
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
Kaoy et al found #HMGCS2 mediates the therapeutic effects of #NAD+ therapy in #HFpEF by restoring normal lipid metabolism & improving mitochondrial function in the heart. https://t.co/snbdYCdtnj @yen_koay @realjosullivan @AshishMisraLab @chenchenwenwen https://t.co/oV5b3cRbOn
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Mashup Score: 1Treg Cells Attenuate Pulmonary Venous Remodeling in PH-LHD via NLRC3 Signaling | Circulation Research - 5 day(s) ago
BACKGROUND: Pulmonary venous remodeling is a key pathological feature of pulmonary hypertension associated with left heart disease (PH-LHD). This study aims to investigate the role of regulatory T (Treg) cells in this process. METHODS: We used mouse models with transverse aortic constriction and cell depletion of Foxp3-DTR/tdTomato mice to examine Treg cells’ function around pulmonary veins in PH-LHD in vivo. To confirm the effect of Nlrc3−/− Treg cells on PH-LHD, we utilized 3 mouse models: Nlrc3 knockout mice, athymic mice, and endothelial cell lineage tracing Cdh5CreERT2+/−-mT/mG+/− mice. The interaction proteins and signaling pathways of Treg cells during endothelial-to-mesenchymal transition were elucidated by protein docking prediction, coimmunoprecipitation and cocultivation of Treg cells with venous endothelial cells. RESULTS: Treg cells were abundant around pulmonary veins of transverse aortic constriction–induced PH-LHD and were essential for promoting inflammation resolution
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
5/5 Treg Cells Attenuate Pulmonary Venous Remodeling in PH-LHD via NLRC3 Signaling by Zhakeer et al https://t.co/KZPRSuq0bj @Tongji_Uni
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Mashup Score: 31Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF | Circulation Research - 6 day(s) ago
BACKGROUND: Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)—a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)—correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates the role of SETD2 in cHFpEF. METHODS: Chromatin immunoprecipitation sequencing and RNA sequencing were used to investigate H3k36me3-related transcriptional regulation. Mice with cardiomyocyte-specific deletion of SETD2 (c-SETD2−/−) were generated and subjected to high-fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Cardiac function and exercise tolerance were assessed by echocardiography and treadmill exhaustion test. A selective pharmacological inhibitor of SETD2, EZM0414, was also tested in cHFpEF mice. Mechanistic experiments were performed in cultured cardiomy
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
Costantino et al found that metabolic stress leads to #chromatin modifications promoting #lipid accumulation and cardiac damage in #HFpEF. Learn more at https://t.co/WOQxOnHiDG @Nazha Hamdani @ODzemali @GoricaEra @Lux_Telesca @LabSantoro https://t.co/6S8JnNJ2Tl
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Mashup Score: 5Novel Truncated Peptide Derived From circCDYL Exacerbates Cardiac Hypertrophy | Circulation Research - 7 day(s) ago
BACKGROUND: Circular RNAs (circRNAs) have been gradually revealed to regulate the progression of heart disease in depth, showing their clinical significance. However, a mass of cardiac circRNAs still has not been functionally characterized. We aimed to explore the potential candidates that are involved in pathological cardiac hypertrophy. METHODS: Public substantial RNA-sequencing data of cardiac circRNAs were utilized to search the cardiac hypertrophy–related circRNAs. Cardiomyocyte hypertrophy in vitro was induced by Ang II (angiotensin II) treatment. Mice were subjected to Ang II infusion to induce cardiac hypertrophy in vivo. Gain-of-function and loss-of-function assays were conducted to detect the effect of RNAs or proteins in cardiac hypertrophy. RESULTS: A circRNA derived from the cdyl (chromodomain Y-like) gene was screened out and named circCDYL. Our results showed that the expression of circCDYL in primary rat cardiomyocytes was significantly induced by Ang II. Gain-of-functi
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
Li & colleagues found increased expression of a circular RNA generated by cdyl (#CircCDYL) in cardiomyocytes aggravates #CardiacHypertrophy. Learn more at https://t.co/8ue3vf3n6Y https://t.co/mMm5adNXhw
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Mashup Score: 1Treg Cells Attenuate Pulmonary Venous Remodeling in PH-LHD via NLRC3 Signaling | Circulation Research - 7 day(s) ago
BACKGROUND: Pulmonary venous remodeling is a key pathological feature of pulmonary hypertension associated with left heart disease (PH-LHD). This study aims to investigate the role of regulatory T (Treg) cells in this process. METHODS: We used mouse models with transverse aortic constriction and cell depletion of Foxp3-DTR/tdTomato mice to examine Treg cells’ function around pulmonary veins in PH-LHD in vivo. To confirm the effect of Nlrc3−/− Treg cells on PH-LHD, we utilized 3 mouse models: Nlrc3 knockout mice, athymic mice, and endothelial cell lineage tracing Cdh5CreERT2+/−-mT/mG+/− mice. The interaction proteins and signaling pathways of Treg cells during endothelial-to-mesenchymal transition were elucidated by protein docking prediction, coimmunoprecipitation and cocultivation of Treg cells with venous endothelial cells. RESULTS: Treg cells were abundant around pulmonary veins of transverse aortic constriction–induced PH-LHD and were essential for promoting inflammation resolution
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
5/5 Treg Cells Attenuate Pulmonary Venous Remodeling in PH-LHD via NLRC3 Signaling by Zhakeer et al https://t.co/KZPRSuq0bj @Tongji_Uni
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Mashup Score: 8Srsf3-Dependent APA Drives Macrophage Maturation and Limits Atherosclerosis | Circulation Research - 7 day(s) ago
BACKGROUND: Circulating monocytes largely contribute to macrophage buildup in atheromata, which is crucial for clearing subendothelial LDLs (low-density lipoproteins) and dead cells; however, the transitional trajectory from monocytes to macrophages in atherosclerotic plaques and the underlying regulatory mechanism remain unclear. Moreover, the role of alternative polyadenylation, a posttranscriptional regulator of cell fate, in monocyte/macrophage fate decisions during atherogenesis is not entirely understood. METHODS: To identify monocyte/macrophage subtypes in atherosclerotic lesions and the effect of alternative polyadenylation on these subtypes and atherogenesis, single-cell RNA sequencing, 3′-end sequencing, flow cytometric, and histopathologic analyses were performed on plaques obtained from Apoe−/− mouse arteries with or without myeloid deletion of Srsf3 (serine/arginine-rich splicing factor 3). Cell fractionation, polysome profiling, L-azidohomoalanine metabolic labeling assay
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
Yang et al reveals that #Srsf3-dependent generation of long 3′ UTR is required for efficient mitochondrial translation, which promotes mature phagocytic #macrophage formation & protects against #atherosclerosis at https://t.co/IkEVtrV1lW @Yancy_y66 @wei_yuanyu23999 https://t.co/55GRvsY0YN
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Mashup Score: 13PCSK9 Regulates Cardiac Mitochondrial Cholesterol by Promoting TSPO Degradation | Circulation Research - 7 day(s) ago
BACKGROUND: Cholesterol is critical for mitochondrial membrane structure and function. Given the emergence of mitochondria as a key factor in the pathogenesis of heart failure, mitochondrial cholesterol homeostasis may be crucial for maintaining mitochondrial properties and thus cardiac function. We previously showed that CM-Pcsk9–/– mice (mice with cardiomyocyte-specific deletion of the gene encoding PCSK9 [proprotein convertase subtilisin-kexin type 9]) have impaired cardiomyocyte mitochondrial bioenergetics and heart function, paralleled by cardiomyocyte mitochondrial cholesterol accumulation and an increased number of mitochondria–endoplasmic reticulum contacts. However, the mechanisms linking PCSK9 to mitochondrial cholesterol homeostasis remain unclear. We hypothesized that PCSK9 acts on proteins involved in mitochondrial cholesterol trafficking in the heart to maintain cardiac mitochondrial function. METHODS: By performing RNA sequencing and immunoblot on hearts from CM-Pcsk9–/–
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
Laudette & colleagues identified a role of #PCSK9 in the regulation of mitochondrial membrane #cholesterol homeostasis. Learn about a promising therapeutic approach for #HeartFailure at https://t.co/PyfZG78Q56 https://t.co/Fod8JIrcqX
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Mashup Score: 19Discover Circ Res May 2025 | AHA Podcasts - 7 day(s) ago
This month on Episode 72 of Discover CircRes, host Cindy St. Hilaire highlights four articles featured in the April 25th and May 9th issues of Circulation Research. This Episode also includes a discussion with Dr. Sarah Costantino and Dr. Francesco Paneni from University Hospital Zurich about their study, Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF This month on Episode 72 of Discover CircRes, host Cindy St. Hilaire highlights four articles featured in the April 25th and
Source: www.ahajournals.orgCategories: General Medicine NewsTweet-
1/5 New @CircRes podcast #DiscoverCircRes https://t.co/qeE1QIIZLv @StHilaireLab chats with @francescopaneni and Sarah Costantino about their study Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF https://t.co/i2w3Lfv1XY @UZH_en https://t.co/fVbzLDKmOA
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@CircRes May 23rd Issue is Out! Compendium on Interorgan Crosstalk in Heart Failure and Cardiometabolic Diseases In this issue read 14 reviews & 5 Research Letters: https://t.co/STHYRFUtry @gabrieleschiat1 @mkontari https://t.co/Z6XrYiQDQl