Current Opinion in Physiology最新文献

Catecholamines (CAs) bind and activate adrenergic receptors (ARs), thus exuding a key role in cardiac adaptations to global physiological queues. Prolonged exposure to high levels of CAs promotes deleterious effects on the cardiovascular system, leading to organ dysfunction and heart failure (HF). In addition to the prominent role of ARs in inotropic and chronotropic responses, recent studies have delved into elucidating mechanisms contributing to CA toxicity and cell death. Central to this process is understanding the involvement of α1AR and βAR in cardiac remodeling and mechanisms of cellular survival. Here, we highlight the complexity of AR signaling and the fundamental need for a better understanding of its contribution to oxidative stress and cell death. This crucial informational nexus remains a barrier to the development of new therapeutic strategies for cardiovascular diseases.

In the brain, mitochondrial components are released into the extracellular space via several mechanisms, including a recently identified type of extracellular vesicles called mitovesicles. While vesiculation of neuronal mitochondria yields various intracellular types of vesicles, with either a single or a double membrane, mitovesicles secreted into the extracellular space are a unique subtype of these mitochondria-derived vesicles, with a double membrane and a specific set of mitochondrial DNA, RNA, proteins, and lipids. Based on the most relevant literature describing mitochondrial vesiculation and mitochondrial exocytosis, we propose a model for their secretion when the amphisomes, a hybrid endosome–autophagosome organelle, fuse with the plasma membrane, releasing mitovesicles and exosomes into the extracellular space. In aging and neurodegenerative disorders, mitochondrial dysfunction, in association with endolysosomal abnormalities, alter mitovesicle number and content, with downstream effect on brain health.

Cardiometabolic diseases (CMDs) are a leading contributor to worldwide morbidity and mortality. Recent insights into the pathogenesis of CMDs reveal crucial roles of intercellular crosstalk between metabolically active organs and cardiac cells. In this context, extracellular vesicles (EVs), lipid membrane-delimited particles containing diverse cargo (including small and long RNAs, proteins, lipids, and metabolites), and nonvesicular extracellular particles (NVEPs) have emerged as key mediators of cell-to-cell communications. EV cargo can reflect the metabolic state of their cells of origin and affect the function of their target cells. Understanding EV cargo content and function is essential for unraveling the pathophysiology of CMDs. This mini-review describes recent studies on EV-mediated local and interorgan crosstalk in CMDs, focusing on those that lead to atrial and ventricular myopathy, which are hallmarks of atrial fibrillation and heart failure, respectively. Lastly, this review discusses the potential applications of EVs in the diagnostics and therapeutics of these CMDs.

The battle against cancer remains a formidable challenge despite ongoing efforts worldwide. Current treatments are limited, leading to increased interest in personalized approaches, including drug delivery via extracellular vesicles (EVs). EVs are lipid bilayer particles released by cells that play a crucial role in intercellular communication by transferring biological compounds. Recent preclinical studies have demonstrated that EVs are also effective delivery vehicles for other cargo, such as chemotherapeutic drugs, immunotherapeutic agents, or nucleic acid–based therapeutics with improved pharmacokinetics. This review focuses on the latest advances on EVs as drug carriers in cancer therapy, pointing out the current ongoing clinical trials testing the potential of molecules, such as interleukin-12, STING agonists, or KRAS-G12D small interfering RNA. The evolving landscape of EVs in targeted cancer therapeutics holds significant promise for developing safer, personalized, and cell-free therapies.

Kidney diseases pose a significant challenge, lacking effective therapies. Extracellular vesicle (EV)-based therapies have emerged as a novel advanced therapeutic. Particularly, mesenchymal stromal cells (MSC) and their EV are being explored as potential candidates. While MSC-EV therapeutics offer promise, there is a lack of widely standardized potency tests to assess EV effectiveness. Tailoring potency assessment in kidney diseases requires considering multifactorial effects and may necessitate a combination of multiple assays to recapitulate EV function. The design of a matrix of assays will be specific for the chosen disease and will involve specific molecular mechanisms and biological processes. This review highlights recent MSC-EV functional assays focused on modeling kidney disease mechanisms of action.