Nature Reviews Cardiology最新文献

Mitochondria are multifunctional organelles that are important for many different cellular processes, including energy production and biosynthesis of fatty acids, haem and iron–sulfur clusters. Mitochondrial dysfunction leads to a disruption in these processes, the generation of excessive reactive oxygen species, and the activation of inflammatory and cell death pathways. The consequences of mitochondrial dysfunction are particularly harmful in energy-demanding organs such as the heart. Loss of terminally differentiated cardiomyocytes leads to cardiac remodelling and a reduced ability to sustain contraction. Therefore, cardiomyocytes rely on multilayered mitochondrial quality control mechanisms to maintain a healthy population of mitochondria. Mitochondrial chaperones protect against protein misfolding and aggregation, and resident proteases eliminate damaged proteins through proteolysis. Irreparably damaged mitochondria can also be degraded through mitochondrial autophagy (mitophagy) or ejected from cells inside vesicles. The accumulation of dysfunctional mitochondria in cardiomyocytes is a hallmark of ageing and cardiovascular disease. This accumulation is driven by impaired mitochondrial quality control mechanisms and contributes to the development of heart failure. Therefore, there is a strong interest in developing therapies that directly target mitochondrial quality control in cardiomyocytes. In this Review, we discuss the current knowledge of the mechanisms involved in regulating mitochondrial quality in cardiomyocytes, how these pathways are altered with age and in disease, and the therapeutic potential of targeting mitochondrial quality control pathways in cardiovascular disease.

Communication between multicellular organs is essential to propagate signals and coordinate their function. Over the past decade, the role of extracellular vesicles in the molecular communication between cells in both physiological and pathological settings has received much attention. Extracellular vesicles can shuttle proteins, lipids and nucleic acids (such as RNA) between cells, thus inducing an array of functional changes in the recipient cells. In this Review, we describe the different extracellular vesicle subclasses and their heterogeneous nature, provide insights into extracellular vesicle-mediated signalling in the cardiovascular system, and highlight how extracellular vesicles can be used as diagnostic and prognostic biomarkers for a variety of pathological conditions. Finally, we also discuss the potential therapeutic applications of extracellular vesicles.

The neural and cardiovascular systems are pivotal in regulating human physiological, cognitive and emotional states, constantly interacting through anatomical and functional connections referred to as the brain–heart axis. When this axis is dysfunctional, neurological conditions can lead to cardiovascular disorders and, conversely, cardiovascular dysfunction can substantially affect brain health. However, the mechanisms and fundamental physiological components of the brain–heart axis remain largely unknown. In this Review, we elucidate these components and identify three primary pathways: neural, mechanical and biochemical. The neural pathway involves the interaction between the autonomic nervous system and the central autonomic network in the brain. The mechanical pathway involves mechanoreceptors, particularly those expressing mechanosensitive Piezo protein channels, which relay crucial information about blood pressure through peripheral and cerebrovascular connections. The biochemical pathway comprises many endogenous compounds that are important mediators of neural and cardiovascular function. This multisystem perspective calls for the development of integrative approaches, leading to new clinical specialties in neurocardiology.

Endomyocardial fibrosis, first described >75 years ago, is a cause of restrictive cardiomyopathy with an unclear aetiopathogenesis that is most commonly found in children and adolescents from tropical regions of Africa, Asia and South America. The epidemiological trends of this cardiomyopathy are difficult to ascertain. The characteristic hallmark of endomyocardial fibrosis is ventricular fibrosis that causes diastolic dysfunction and atrioventricular regurgitation. Although advances in medical treatment for heart failure and more tailored surgical techniques to treat the condition have increased survival, the outcomes in affected patients remain poor. A major focus of research is the identification of biomarkers of preclinical disease and new therapeutic targets. Collaborative multidisciplinary research and cross-learning from other fibrotic conditions should impart knowledge and help to improve the survival rates and the quality of life of patients with endomyocardial fibrosis.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease in individuals with or without hypertension. However, the mechanisms and management of SSBP remain unclear, mainly because the diagnosis of this condition relies on salt loading–depletion protocols that are not feasible in the clinic. The prevalence of hypertension is lower in premenopausal women than in men, but this sex-specific difference is reversed after menopause. Whether excessive SSBP in women at any age contributes to this reversal is unknown, but many clinical studies that have rigorously assessed for SSBP using salt loading–depletion protocols have confirmed that SSBP is more prevalent in women than in men, including during premenopausal age. In this Review, we discuss sex-specific mechanisms of SSBP. We describe sex-related differences in renal transporters, hypertensive pregnancy, SSBP in autoimmune disorders and mitogen-activated protein kinase signalling pathways, and highlight limitations and lessons learned from Dahl salt-sensitive rat models.

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.

With advances in materials science and medical technology, wearable sensors have become crucial tools for the early diagnosis and continuous monitoring of numerous cardiovascular diseases, including arrhythmias, hypertension and coronary artery disease. These devices employ various sensing mechanisms, such as mechanoelectric, optoelectronic, ultrasonic and electrophysiological methods, to measure vital biosignals, including pulse rate, blood pressure and changes in heart rhythm. In this Review, we provide a comprehensive overview of the current state of wearable cardiovascular sensors, focusing particularly on those that measure blood pressure. We explore biosignal sensing principles, discuss blood pressure estimation methods (including machine learning algorithms) and summarize the latest advances in cuffless wearable blood pressure sensors. Finally, we highlight the challenges of and offer insights into potential pathways for the practical application of cuffless wearable blood pressure sensors in the medical field from both technical and clinical perspectives.

Correction to: Nature Reviews Cardiology https://doi.org/10.1038/s41569-025-01123-4, published online 21 January 2025.