Michael Raddatz

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...

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

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9/9
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...

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...

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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. 🤔

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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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.

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

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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. 💭

Table summarizing baseline cardiac metrics

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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. 😮‍💨

Trial flow diagram

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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. 🚴📆

Table describing baseline characteristics of patients in the trial

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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.

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 ...

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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. 🫀💪

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

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! 🧵
1/9
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Photo of Senator Chris Van Hollen with Kilmar Abrego Garcia.

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.

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

Great manuscript and very informative figures!

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10/10
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...

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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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. 📈

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

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

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

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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.

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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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.

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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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.

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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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. 🧫

Seahorse assay showing decreased respiratory capacity in diseased AVICs. Bar charts showing decresaed ATP production, coupling efficiency, and mitochondrial staining with MitoTracker.

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The authors use a model system of aortic valve interstitial cells (AVICs) isolated from humans with and without calcific aortic valve disease (CAVD). They show that mitochondrial respiration, ATP production, coupling efficiency, and mitochondrial mass are all ⬇️ in diseased AVICs. 🪫

Title page of a paper titled Spermidine Enhances Mitochondrial Function and Mitigates Aortic Valve Calcification

In these uncertain times, celebrating novel science is one way to stay grounded and hopeful. In this month’s issue of #JACCBTS, Song, et al. investigate mitochondrial function in aortic valve calcification. Join me to see what they found! 🧵
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Mike spotted this before the rest of us. 🫡

Publications from 2025 are shared more on Bluesky than on X/Twitter.

I have confirmation from several sources now that all T32s, many F30s and F31s, and most or all Center awards (P30, P50) have been terminated at Columbia.

This is quite damaging to research and to individuals.

This is pure terrorism and cannot be legal. But litigation will take time...

Trump Pulled $400 million From Columbia. Other Schools Could Be Next. The administration has circulated a list that includes nine other campuses, accusing them of failure to address antisemitism.

List includes Harvard University, George Washington University, Johns Hopkins University, New York University, Northwestern University, the University of California, Los Angeles; the University of California, Berkeley, the University of Minnesota, and the University of Southern California.

NIH budget: $ 48b
Musk wealth: $351b

Both are mostly funded by your tax dollars

But only one might save your life
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During Rare Disease Week, patients and advocates were in D.C. for an event with the NIH, FDA, and HHS to highlight work being done on treatments and cures. It was abruptly canceled. Why? The administration fired the people organizing this important event and advancing this work.