Weill Cornell Medicine’s Post

Hypertension's hidden hand: Pressure-driven foam cell formation revealed as key driver of arterial disease A new study unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. A new study in Advanced Science unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. Led by Professor Thomas Iskratsch, Professor of Cardiovascular Mechanobiology & Bioengineering at Queen Mary University of London, the research team exposes a novel mechanism by which elevated pressure transforms muscle cells in the arterial wall into "foam cells" -- the building blocks of plaque buildup that cripples arteries. The study focuses on vascular smooth muscle cells (VSMCs), the workhorses responsible for maintaining blood vessel tone and flow. Under the chronic stress of hypertension, VSMCs undergo a dramatic makeover. The researchers discovered that pressure alone triggers these cells to fill with lipid droplets, morphing them into foam cells -- culprits in the formation of atherosclerotic lesions, the hallmark of arterial disease. "This finding is pivotal because VSMCs make up over half of the foam cells found in arterial blockages," explains Professor Iskratsch. "Understanding how pressure flips this switch from muscle to foam cell is crucial for developing new therapies to control or reverse the buildup of these dangerous lesions." The study goes deeper, identifying the molecular machinery behind pressure's impact. Using advanced imaging techniques, researchers pinpointed a "mechanosignalling" pathway involving Piezo1, a pressure-sensitive protein, as well as changes in lipid metabolism and gene activity. This paves the way for novel therapies targeting specific pressure-sensitive points in the cell. This breakthrough research offers not only a deeper understanding of arterial disease but also exciting possibilities for future treatment strategies. By targeting the mechanisms that drive VSMC transformation into foam cells, researchers might be able to develop medications that prevent or even shrink atherosclerotic lesions. "Our findings provide a vital blueprint for developing next-generation therapies that could benefit millions suffering from the life-threatening consequences of arterial disease," concludes Professor Iskratsch. "This is a significant step forward in our journey towards a future where high blood pressure doesn't have to steal away life." #unitofbharat #vsmc #atherosclerotic #arterial #Hypertension #therapies #foamcells

Really interesting article characterizing a subclass of neuroendocrine cells (NECs) in the larynx and trachea. NECs in the airway sense environmental stimuli, release signaling molecules, and interact with and stimulate peripheral nerves. The functional roles of NECs in the healthy lung, trachea, and larynx had not been fully elucidated. Here, the authors use an elegant mouse model to show that tracheal and laryngeal NECs protect the airway by triggering swallowing and cough-like behaviors in response to aspirated noxious stimuli such as water and acid. Mechanisms discovered include the involvement of Piezo-type mechanosensitive ion channel component 2 (PIEZO2) in mechanical sensation and that activated NECs produce ATP to activate purinoreceptive sensory neurons that initiate swallowing and cough reflexes. This work both reveals new biology of NECs and target cells for the development of therapeutic interventions for respiratory disorders. Indeed, therapeutics that target puronergic receptors in the airway are under development. https://lnkd.in/ggufHDAa

Engineering Brain-Derived Exosomes to Target Mitochondria Holds Promise in Treating Neurodegenerative Diseases! Mitochondrial dysfunction is linked to various health conditions, including cardiovascular and neurodegenerative diseases. Targeting mitochondrial function through exosome-based therapy presents a potential solution. Lanrong Bi, zhiying Shan and their team at Michigan Technological University have developed a novel technique to engineer brain-derived exosomes that specifically target mitochondria within brain cells. Initial tests on primary neuron cells and healthy rats have shown promising results, signifying a significant advancement in treating these debilitating conditions. 🔗 Read more: https://lnkd.in/dEQa8Z6g Join us at Targeting EVs 2024 in Malta this October, where Dr. Bi will present their latest research on engineering exosomes for precise mitochondrial targeting in brain cells. 🌐 Conference Details: https://lnkd.in/dMm8jZjd #TargetingExtracellularVesicles #TargetingEVs #extracellularvesicles #evs #exosomes #exosome #microbiome #microbiota #redox #iron #homeostasis #skin #mitochondria #ISM #WMS

Hypertension's hidden hand: Pressure-driven foam cell formation revealed as key driver of arterial disease A new study unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. A new study in Advanced Science unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. Led by Professor Thomas Iskratsch, Professor of Cardiovascular Mechanobiology & Bioengineering at Queen Mary University of London, the research team exposes a novel mechanism by which elevated pressure transforms muscle cells in the arterial wall into "foam cells" -- the building blocks of plaque buildup that cripples arteries. The study focuses on vascular smooth muscle cells (VSMCs), the workhorses responsible for maintaining blood vessel tone and flow. Under the chronic stress of hypertension, VSMCs undergo a dramatic makeover. The researchers discovered that pressure alone triggers these cells to fill with lipid droplets, morphing them into foam cells -- culprits in the formation of atherosclerotic lesions, the hallmark of arterial disease. "This finding is pivotal because VSMCs make up over half of the foam cells found in arterial blockages," explains Professor Iskratsch. "Understanding how pressure flips this switch from muscle to foam cell is crucial for developing new therapies to control or reverse the buildup of these dangerous lesions." The study goes deeper, identifying the molecular machinery behind pressure's impact. Using advanced imaging techniques, researchers pinpointed a "mechanosignalling" pathway involving Piezo1, a pressure-sensitive protein, as well as changes in lipid metabolism and gene activity. This paves the way for novel therapies targeting specific pressure-sensitive points in the cell. This breakthrough research offers not only a deeper understanding of arterial disease but also exciting possibilities for future treatment strategies. By targeting the mechanisms that drive VSMC transformation into foam cells, researchers might be able to develop medications that prevent or even shrink atherosclerotic lesions. #unitofbharat #vsmc #Hypertension #gene #molecular #atherosclerotic #arterial

MITO NEWS: A recent study by Jose Romero et. al of University of Birmingham dives into mitochondrial quality control (MQC), shedding light on possible novel therapeutic approaches. Restoration of MQC has shown promise in conferring neuroprotection in various conditions, including DR. However, understanding the intricate interplay between MQC mechanisms (dynamics, mitophagy, biogenesis) during disease progression is crucial for effective interventions. Leveraging next-gen reporters like Mito-QC, the team unraveled how mitochondrial turnover is impaired in DR, paving the way for targeted therapies. The study unveiled mitochondrial hyperfusion as a key player in DR pathology, hindering turnover and exacerbating neurodegeneration. N6-furfuryladenines, particularly in glycosylated form (KR), emerge as potential game-changers, restoring turnover and offering neuroprotection independently of glycemic status. These compounds show promise in tuning-up mitochondrial health, essential for protecting retinal neurons. The study also highlights neurodegenerative changes in the human diabetic retina, emphasizing the importance of protecting photoreceptors and their synaptic machinery. By targeting mitochondrial turnover, the researchers aim to provide innovative solutions for DR prevention and treatment. Learn more: https://lnkd.in/eSHUM_Uc Authors: Janet Lord, Parth Narendran, Tim Curtis, Ian Ganley & Aidan Anderson

📃Scientific paper: Potential role of recombinant growth differentiation factor 11 in Alzheimer’s disease treatment Abstract: Alzheimer's disease (AD) is a neurodegenerative disease closely related to the accumulation of beta-amyloid (Aβ) plaques. Growth differentiation factor 11 (GDF11) is one of the proteins that play a role in the aggravation of AD. Decreased concentration of GDF11 disrupts regenerative nervous system, blood vessels, and various vital systems. Low levels of GDF11 with age can be overcome with recombinant GDF11 (rGDF11) to rejuvenate the regenerative effect. Based on research results, rGDF11 enhance the proliferation rate of neuronal precursor cells as well as angiogenesis. rGDF11 can replace lost levels of GDF11, overcome astrogliosis and activation of nerve cell microglia. Therapeutic effect of rGDF11 leads to an improved prognosis in AD patients by neurogenesis and angiogenesis. The prospects of rGDF11 in the treatment of AD have great potential for further research in the future. Discover the rest of the scientific article on es/iode ➡️https://etcse.fr/W8Qc #alzheimer #science #health

The company's leading drug candidate in the NeuroRestore platform NeuroRestore platform shows, among other things, positive effects on mitochondrial function, something that is disturbed in neurodegenerative diseases such as Alzheimer’s. These preclinical studies also seem to indicate that substance treatment leads to increased survival of the nerve cells. During 2022 and 2023, the studies have been complemented with additional data on the neuroprotective, regenerative, and long-term effects of ACD856. Furthermore, the data show that ACD856 increases the amount of a specific protein in the neurites that plays an important role in nerve cell communication, something that is strongly affected in the disease. These important data, which further strengthen NeuroRestore’s potential as a disease-modifying treatment in Alzheimer’s diseases, have been presented at several scientific conferences during the last two years. There is also strong scientific support for this target mechanism in depression. NeuroRestore substances have had effects in preclinical models of depression which are further supported by data in recent articles in the reputable journals Cell , Nature and Science . These studies show that several different classes of antidepressants appear to mediate their effects via BDNF/TrkB, further strengthening the link between BDNF and depression. AlzeCure has been able to show in preclinical models that NeuroRestore substances have antidepressant effects and that they also release signaling substances in the brain that are relevant for depression. Learn and read more about our candidate: https://lnkd.in/e6BR563C #alzheimers #alzecure #Alzheimerfonden #alzeheimer #depression #mentalhealthmatters #science #neurorestore #ACD856

"Unlocking the Therapeutic Potential of Mitochondria" Excited to announce our new research paper in #Nature paper! This study was conducted when I was in the Melero-Martin Lab at Boston Children's Hospital and Harvard Medical School We show that transplanting mitochondria into endothelial cells boosts their ability to form blood vessels in ischemic tissues, with mitophagy as the key mechanism - a potential game-changer for vascular cell therapies. Read more at: https://lnkd.in/ed3nCKcY Mitochondrial dysfunction is a common denominator in both biological aging and many diseases. While mitochondria originated from endosymbiotic bacteria billions of years ago, they remain mobile and can move between cells and organs in our bodies. This process, known as Mitochondrial Transfer (MitoT), is essential not only for maintaining hemostasis, but also for repairing damaged tissues. The therapeutic potential of MitoT is immense. Administering isolated mitochondria enables us to utilize its cytoprotective advantages, rejuvenating damaged cells, restoring cellular functions, and regulating immune responses. Encouraging pre-clinical and clinical trials across various institutions have shown promising results in treating conditions including myocardial infarction, ischemic stroke, acute kidney injury, pulmonary fibrosis, and obesity. In this very exciting new field, many underlying mechanisms of MitoT remain elusive. However, gaining a deeper understanding of how MitoT works will significantly reduce resistance to its clinical implementation. In our recent paper in #Nature, we showcased MitoT as a form of cell-to-cell communication within the vascular system. Under stressful conditions, cells transferred mitochondria to their neighbors, boosting their bioenergetics and overall fitness. Intriguingly, this process didn't hinge on transferring fully functional mitochondria. Instead, the transferred mitochondria acted as a catalyst for mitophagy, elucidating how a small number of exogenous mitochondria could notably enhance ATP production in recipient cells. Read more of this Nature Article at: https://lnkd.in/ed3nCKcY Nature Commentary article: https://lnkd.in/gYVVQhUb   STAT News coverage: https://lnkd.in/gt_wxzWf #RegenerativeMedicine #mitophagy #mitochondria #vasculature

🦋Favourite paper of the day 🦋 Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity The insulin-like growth factor pathway (IGF1) regulates cellular metabolism and aging. However, the effects of attenuated IGF1 signaling on cardiac aging remain controversial. This study shows a link between IGF1 signaling and cardiac aging. Enhanced IGF1R signaling in young mice causes early cardiac decline and reduced lifespan, while attenuated signaling improves cardiac function during aging and increases lifespan. These findings have implications for the development of targeted therapies for older adults. #Aging #IGF1 #autophagy 

the RACP program is based mainly on support and prevention in order to avoid having to seek treatment (difficulty, pain, cost)