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Reposted by Michael Raddatz

University of California @uofcalifornia.bsky.social · Aug 8

The federal government’s demand of $1 billion from @UCLA would devastate the nation’s best public university, cut off life-saving care, halt tech and economic growth and reduce educational access.

Stand with UC to protect our vital mission: www.universityofcalifornia.edu/get-involved...

Stand Up for UC

www.universityofcalifornia.edu

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Reposted by Michael Raddatz

Jaweed Kaleem @jaweedkaleem.bsky.social · Aug 8

BREAKING: The Trump administration is seeking $1 billion+ from the University of California to restore UCLA's frozen federal funding. The payout would far exceed any made by universities so far. UC has not agreed to it, sources say. www.latimes.com/california/s...

Trump seeking $1 billion fine from UCLA over antisemitism allegations

The Trump administration has proposed the University of California pay more than a $1 billion to settle antisemitism charges and restore frozen grant funding at UCLA.

www.latimes.com

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Reposted by Michael Raddatz

Boback Ziaeian @boback.bsky.social · Aug 1

Trump freezes $200 million in UCLA science and medical research funding, citing antisemitism www.latimes.com/california/s... @latimes.com

Trump freezes $200 million in UCLA science and medical research funding, citing antisemitism

The Trump administration has frozen roughly $200 million in National Science Foundation, National Institutes of Health and other federal agency-funded research at UCLA, citing allegations the school d...

www.latimes.com

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Michael Raddatz @michaelraddatz.bsky.social · May 28

@jeffhsumd.bsky.social
@vascularimmuno.bsky.social
@jeanwassenaar.bsky.social

Michael Raddatz @michaelraddatz.bsky.social · May 28

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In summary, IL-6 may play a beneficial role in cardiovascular adaptation, and this may impact cardiovascular adaptation to exercise in patients taking an IL-6 inhibitor for RA. Read the full paper in this month’s issue of #JACCBTS! doi.org/10.1016/j.ja...

Redirecting

doi.org

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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Given the reported beneficial effects of IL-6i in coronary disease (doi.org/10.1016/j.ja...) & ongoing related trials in cardiovascular patients (e.g., clinicaltrials.gov/study/NCT061...), this work reminds us that IL-6 biology is complex. There may be a right time, place, & amount for IL-6. 🤔

The clinical significance of interleukin‐6 in heart failure: results from the BIOSTAT‐CHF study

Aims Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-α were largely unsuccessful. Interleukin (IL)-6 is an important...

doi.org

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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While the LV mass and stroke volume increases were only significant in the TNFi group, only the IL-6i group had a significant ⬆️ in relative VO2 peak. This is counterintuitive given the role of cardiac output in VO2, but may be explained by positive effects of IL-6i outside of cardiac remodeling.

Table showing an increase in LVM, LVSV, and LVEDV in the TNFi group, and n increase in VO2 in the IL-6i group.

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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After 12 weeks of exercise, they underwent repeat testing. There was a physiologic ⬆️ in LV mass in the exercise group among those using a TNFi, but not among those using an IL-6i. This supports the authors’ hypothesis that IL-6 signaling is important for exercise adaptation in RA patients. 💭

Dot plot showing an increase in LV mass among exercise patients in those receiving a TNFi

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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Prior to the exercise regimen, patients underwent cardiac MRI and metabolic testing. As seen here and further summarized in the full manuscript, patients had normal cardiac MRI metrics, low rates of cardiac comorbidities, and below average fitness as measured by VO2 peak. 😮‍💨

Table summarizing baseline cardiac metrics

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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Patients were then randomized, with half of the patients undergoing supervised 45-minute exercise sessions on an ergometer bicycle three times a week in addition to their usual activity. 🚴📆

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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They enrolled pts 18-69 yrs old with RA stably treated with a TNFi or IL-6i for >4 months. Their RA had to be well-controlled ✅ measured by DAS28-ESR score & minimal corticosteroid use. Importantly, pts receiving IL-6i had more often & more frequently tried other prior biologics for RA control.

Table describing baseline characteristics of patients in the trial

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Michael Raddatz @michaelraddatz.bsky.social · May 28

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Given previously described beneficial effects of IL-6 during exercise (onlinelibrary.wiley.com/doi/10.1111/...), the authors hypothesized that patients receiving TNF inhibitors would see more beneficial cardiovascular adaptation from guided exercise than those receiving IL-6 inhibitors. 🫀💪

Anti‐inflammatory effects of exercise: role in diabetes and cardiovascular disease

Background Persistent inflammation is involved in the pathogenesis of chronic diseases such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Aims The aim of this review was to ...

onlinelibrary.wiley.com

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Michael Raddatz @michaelraddatz.bsky.social · May 28

In this month’s issue of #JACCBTS, Jønck, et al. explore the effects of cytokine inhibitors on cardiovascular adaptability in rheumatoid arthritis (RA). Read below to see what they found! 🧵
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@jaccjournals.bsky.social

Title page of a paper titled IL-6 inhibitors and TNF inhibitors: Impact on Exercise-induced Cardiac Adaptations in Patients With Rheumatoid Arthritis

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Reposted by Michael Raddatz

Senator Chris Van Hollen @vanhollen.senate.gov · Apr 18

I said my main goal of this trip was to meet with Kilmar. Tonight I had that chance. I have called his wife, Jennifer, to pass along his message of love. I look forward to providing a full update upon my return.

Photo of Senator Chris Van Hollen with Kilmar Abrego Garcia.

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Reposted by Michael Raddatz

Boback Ziaeian @boback.bsky.social · Mar 31

The Lancet Commission on rethinking coronary artery disease: moving from ischaemia to atheroma

Excited to have contributed to this work. #AHA25
www.thelancet.com/commissions/... @thelancet.bsky.social

The Lancet Commission on rethinking coronary artery disease: moving from ischaemia to atheroma

www.thelancet.com

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Michael Raddatz @michaelraddatz.bsky.social · Mar 31

Great manuscript and very informative figures!

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

@jeffhsumd.bsky.social @vascularimmuno.bsky.social @jeanwassenaar.bsky.social

Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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In summary, diseased AVICs have mitochondrial dysfunction, and spermidine supplementation or DNMT1 inhibition might hold promise as therapeutics to reverse this process and treat valve calcification. Read the full paper in this month’s issue of #JACCBTS! www.sciencedirect.com/science/arti...

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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The authors finally attempted to treat this same pathway through DNMT1 inhibition. They show that DNMT1 is ⬆️ with disease in human valves, as anticipated. Use of a DNMT1 inhibitor (5-Azacytidine) in diseased human AVICs increases SIRT1, PPARG, and markers of mitochondrial biogenesis. 📈

Human valve IHC showing increased DNMT1 expression in disease.

Box plots showing increase of DNMT1 and decrease of SIRT1, PPARG, and PGC1a in diseased AV cells. This is reversed with 5-AzaC.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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Returning to the initial mitochondrial phenotype, they show that spermidine improves mitochondrial function, even beyond healthy AVIC function. 🪃

Seahorse assay showing decreased respiration in diseased cells. Spermidine treatment augments respiration beyond both healthy and diseased cells. Bar charts showing a similar pattern with ATP production and coupling efficiency.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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Back in the dish, they showed that spermidine induces the same molecular changes in AVICs. 🧫

Box plots showing increased pAKT/AKT and DNMT1 in diseased cells and decreased TP53, SIRT1, and PPARG. These patterns are reversed with spermidine.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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They confirmed the expression patterns of TP53 ⬆️, SIRT1 ⬆️, DNMT1 ⬇️, and PPARG ⬆️ directly in the AVs from mice treated with spermidine or water.

Bar charts showing protein expression data of TP53 increased, SIRT1 increased, DNMT1 decreased, and PPARG increased with spermidine treatment.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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They next performed LC-MS proteomics on AVs from 🐭 with and without spermidine supplementation. They identified activation of the oxidative phosphorylation protein pathway. Further network analysis identified DNMT1 as a ⬇️ node, and PPARG, SIRT1 and TP53 as ⬆️ with spermidine.

Horizontal bar chart showing oxidative phosphorylation as the only positive Z-score protein set.

Network analysis showing DNMT1 and PPARG relationship and confidently predicted inhibition and activation respectively.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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They translated this in vitro finding to an Ldlr-/- and high-fat diet (HFD)-fed 🐭 model of CAVD and found improved echocardiographic metrics of aortic stenosis (AV peak gradient) and ⬇️ valve calcification and fibrosis with spermidine treatment.

Experimental model with an Ldlr-/- mouse treated with HFD and either water or spermidine. Box plots show increasing peak gradient with aging in the water-treated mice, that is not present in mice treated with spermidine.

Alizarin red staining of aortic valves and bar charts showing increase in AV thickness, MT stain, COL1, and Alizarin red in the Ldlr-/- & HFD disease model that is reversed with spermidine.

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Michael Raddatz @michaelraddatz.bsky.social · Mar 24

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The authors hypothesized that spermidine could be used to augment mitochondrial function (💪 read more: pubmed.ncbi.nlm.nih.gov/29371440/). They first showed that spermidine ⬇️ expression of calcification-related genes, both in diseased AVICs and in osteogenic media. 🧫

Box plots showing increase of ALP, Osteocalcin, RUNX2, and COL1A1 expression in diseased cells, which is reversed with treatment with spermidine. Alizarin red staining shows an increase with osteogenic media that is reversed with spermidine.

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