Current Opinion in Physiology最新文献

Pronounced sex differences in the development and outcome of cardiovascular diseases (CVD) exist. Apolipoprotein A1 (APOA1), the basic structural protein of high-density lipoprotein (HDL), is involved in key metabolic processes. However, its role in the pathogenesis of CVD is incompletely understood. The effects of biological sex on factors influencing the APOA1-lipid balance and the underlying mechanisms are also poorly understood. Here, we summarize evidence supporting sex-biased and sex hormone-dependent regulation of APOA1. In particular, we discuss sex-biased APOA1 genetic variation, sex differences in APOA1 regulation and cardiovascular physiology, and sex hormone-dependent regulation of APOA1 in cis- and transgender individuals. We put forward that studying the effects of biological sex will contribute to a better understanding of the role of APOA1 in cardiovascular physiology and its sex-biased association with CVD. Importantly, in situations of sex hormone therapy or inhibition, more sex-stratified data are required to inform clinical management of APOA1-related cardiovascular risk in a sex-dependent manner.

Preeclampsia (PE) is a multisystem obstetric disorder that affects 2–10% of pregnancies worldwide and a leading cause of maternal and fetal morbidity and mortality. The etiology of PE development is not clearly delineated, but since delivery of the fetus and placenta often leads to symptom resolution in the most cases of PE, it is hypothesized that the placenta is the inciting factor of the disease. Current management strategies for PE focus on treating the maternal symptoms to stabilize the mother in an attempt to prolong the pregnancy. However, the efficacy of this management strategy is limited. Therefore, identification of novel therapeutic targets and strategies is needed. Here, we provide a comprehensive overview of the current state of knowledge regarding mechanisms of vascular and renal pathophysiology during PE and discuss potential therapeutic targets directed at improving maternal vascular and renal function.

The respiratory system is the first step in the transport of oxygen during dynamic exercise. This review outlines the anatomical and functional changes that occur to the respiratory system with healthy aging. Furthermore, we emphasize how age-related changes to the respiratory system may differ on the basis of sex. We outline investigations, both classic and recent, that have made key contributions to our understanding the integrated structure–function relationship of the pulmonary system. We add, what we believe, are considerable gaps and next steps in the field of respiratory exercise physiology.

Macroautophagy, herein referred to as autophagy, has long been implicated in the pathophysiology of neurodegenerative diseases. However, an incomplete understanding of how autophagy contributes to disease pathogenesis has limited progress in acting on this potential target for the development of disease-modifying therapeutics. Research in the past few decades has revealed that autophagy plays a specialized role in the synapse, a site of early dysfunction in multiple neurodegenerative diseases. In this review, we discuss the evidence suggesting that inadequate autophagy at the synapse may contribute to neurodegeneration, and why the functions of autophagy may be particularly relevant for synaptic function.

Preeclampsia remains a major health concern for mother and child. Yet, treatment options remain limited to early delivery. Placental dysfunction in preeclampsia occurs in response to an increase in oxidative stress and inflammatory cytokines with vasoactive and antiangiogenic factors contributing to impaired maternal and fetal health. Moreover, recent studies indicate a potential role for epigenetic mediators in the pathophysiology of placental ischemia. Numerous animal models are utilized to explore the pathogenesis of preeclampsia and fetal growth restriction. This review provides a brief overview of recent progress in preclinical studies regarding potential therapeutic targets for the treatment and prevention of preeclampsia with an emphasis on fetal growth restriction and the fetal programming of increased cardiovascular risk.

Lipids are organic biomolecules that provide structural support to cells, but are also important for energy storage and signaling. Lipid profiling has emerged as a new technology with the potential of identifying new biomarkers and therapeutic targets. The lipid composition of cardiomyocyte membranes is altered during the process of cardiac remodeling, including exercise-induced heart enlargement (physiological cardiac hypertrophy) and disease-induced pathological remodeling. Phosphoinositide 3-kinase (PI3K) is an essential regulator of exercise-induced physiological hypertrophy and mediator of cardioprotection in cardiac stress settings. In this review, we first briefly summarize the protective role of exercise and PI3K on the heart. Next, we describe the regulation of lipids in the heart and circulation by exercise or transgenic expression of PI3K (increased or decreased), and contrast this to cardiac disease settings. We also describe studies in which exercise or PI3K-regulated lipids have been associated with cardiorespiratory fitness or cardioprotection, and discuss potential clinical applications.

Regular exercise improves cardiovascular and metabolic health. The beneficial effects of exercise are influenced by several factors, including exercise intensity, biological sex, and the time-of-day at which exercise is performed. In this short article, we review recent evidence of how exercise influences muscle metabolism and how circadian rhythm impacts tissue adaptations to exercise and exercise performance. Emerging out of these findings is a new appreciation for how nutrient timing and diurnal rhythms could be exploited to maximize the health benefits to exercise, while minimizing cardiovascular event risk.

Hair cells of the mammalian cochlea are specialized mechanosensory cells that convert mechanical stimuli into electrical signals to initiate the neuronal responses that lead to the perception of sound. The mechanoelectrical transduction (MET) machinery of cochlear hair cells is a multimeric protein complex that consists of the pore-forming subunits of the MET channel and several essential accessory subunits that are crucial to regulate channel function and render the channel mechanically sensitive. Mutations have been discovered in the genes that encode all known components of the MET machinery. These mutations cause hearing loss with or without vestibular dysfunction. Some mutations also affect other tissues such as the retina. In this brief review, we will summarize gene mutations that affect the MET machinery of hair cells and how the study of the affected genes has illuminated our understanding of the physiological role of the encoded proteins.