Current Opinion in Physiology最新文献

Angiogenesis, the process of building new vessels, is important in physiology. In addition, it is involved in different pathologies, including cancers, ischemia, macular degeneration and inflammatory bowel disease. The regulation of angiogenesis is multifaceted and according to recent data includes transcriptional modulation by enhancers and non-coding RNAs as well as post-transcriptional regulation by microRNAs. In this review, we highlight recent findings in this field that relate both to physiological and pathological angiogenesis and discuss the effects on key angiogenic factors.

To survive, all organisms must detect and respond to mechanical cues in their environment. Cells are subjected to a plethora of mechanical forces, such as hydrostatic pressure, cell-cell contact, stretch, compression, and shear stress. Mechanosensitive (MS) membrane proteins have evolved across all life kingdoms to sense and respond to forces in the membrane. Bacterial MS ion channels provide a blueprint for understanding the fundamental mechanisms that underpin cellular responses to mechanical signals. Recently, the identification of eukaryotic force transducers, which includes membrane proteins other than channels, has led to the recognition of common structural hallmarks and unified biophysical mechanisms that could potentially link these diverse proteins. Accumulating evidence suggests G protein-coupled receptors (GPCRs) are candidates for pressure sensing in mammals. This review summarises the current knowledge on MS GPCRs, describes the tools used to assess their mechanosensitivity, and aims to highlight the key characteristics that link these receptors to established mechanosensors.

Myocarditis is frequently caused by viral infections, but animal models that closely resemble human disease suggest that virus-triggered autoimmune disease is the most likely cause of myocarditis. Myocarditis is a rare condition that occurs primarily in men under age 50. The incidence of myocarditis rose at least 15x during the coronavirus disease 2019 (COVID-19) pandemic from 1–10 to 150–400 cases/100 000 individuals, with most cases occurring in men under age 50. COVID-19 vaccination was also associated with rare cases of myocarditis primarily in young men under 50 years of age with an incidence as high as 50 cases/100 000 individuals reported for some mRNA vaccines. Sex differences in the immune response to COVID-19 are virtually identical to the mechanisms known to drive sex differences in myocarditis pre-COVID based on clinical studies and animal models. The many similarities between COVID-19 vaccine-associated myocarditis to COVID-19 myocarditis and non-COVID myocarditis suggest common immune mechanisms drive disease.

This review examines how the experience of being a parent affects hippocampal plasticity throughout the lifespan, in both male and female rodents. The hippocampus is a unique region capable of producing new neurons throughout adulthood in numerous mammals. When transitioning into parenthood, there is a significant impact on hippocampal neurogenesis and other forms of plasticity in female and male rodents. However, research on the regulation and functional implications (such as cognitive abilities and anxiety regulation) is limited and mixed. Studies have been conducted across sexes, ages, and species. The effects of motherhood on the hippocampus are well-documented in monoparental laboratory rats, while research on fatherhood is more limited. Biparental species provide an opportunity to study this experience in both sexes. We review the current knowledge and propose future research questions to increase our understanding of the short- and long-term consequences of parenthood in both sexes.

Endothelial caveolae are essential for a wide range of physiological processes and have emerged as key players in vascular biology. Our understanding of caveolar biology in endothelial cells has expanded dramatically since their discovery, revealing critical roles in mechanosensation, signal transduction, eNOS regulation, lymphatic transport, and metabolic disease progression. Furthermore, caveolae are involved in the organization of membrane domains, regulation of membrane fluidity, and endocytosis which contribute to endothelial function and integrity. Additionally, recent advances highlight the impact of caveolae-mediated signaling pathways on vascular homeostasis and pathology. Together, the diverse roles of caveolae discussed here represent a breadth of cellular functions presenting caveolae as a defining feature of endothelial form and function. In light of these new insights, targeting caveolae may hold potential for the development of novel therapeutic strategies to treat a range of vascular diseases.

The complex and hierarchical vascular network of arteries, veins, and capillaries features considerable endothelial heterogeneity, yet the regulatory pathways directing arteriovenous specification, differentiation, and identity are still not fully understood. Recent advances in analysis of endothelial-specific gene-regulatory elements, single-cell RNA sequencing, and cell lineage tracing have both emphasized the importance of transcriptional regulation in this process and shed considerable light on the mechanism and regulation of specification within the endothelium. In this review, we discuss recent advances in our understanding of how endothelial cells acquire arterial and venous identity and the role different transcription factors play in this process.

In the human heart, adrenaline activates the β₂-adrenoceptor (β₂AR) to cause powerful increases in contractile force and acceleration of contraction. This is explained by tight coupling of the β₂AR to the Gsα-protein–cyclic AMP–PKA signaling pathway with phosphorylation of proteins, including the L-type Ca²⁺ channel, ryanodine receptor, phospholamban, and sarcomeric proteins troponin I and C-protein. Experimentally, it has been shown that activation of β₂ARs is arrhythmogenic in the human failing heart. From cell- and animal model-based experiments, there is increased awareness of the broader signaling repertoire of the β₂AR. The β₂AR has the ability to couple simultaneously to Gsα- and Giα-proteins and activate β-arrestin signaling pathways. In addition to the orthosteric binding site, modes of conformation stabilization exist through the allosteric binding site and with pepducins. Beneficial effects, including cardioprotection, have been observed, waiting for translation to the human diseased heart and fuelling optimism for advancement of therapeutics for heart disease.

Adrenergic receptors (ARs) and catalytic receptors (CRs), two major classes of cell-surface receptors, play essential roles in a wide range of physiological and pathological processes. Studies over the years have revealed that ARs and CRs, along with their associated signaling transduction pathways, are not isolated in the cells. Instead, there exists functional crosstalk, involving either activation or inhibition, among specific members of ARs and CRs. Although the dynamics and mechanism of individual receptors within each family have been extensively studied, we have just begun to understand the spatiotemporal dynamics, functional consequences, and underlying mechanisms of the crosstalk between ARs and CRs. In this review, we will provide a concise overview of recent progress in identifying and elucidating the crosstalk, either unidirectional or bidirectional, between ARs and CRs.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is diagnosed by the presence of two of the following three characteristics: hyperandrogenemia and/or hyperandrogenism, oligo-/amenorrhea, and polycystic ovarian morphology. PCOS is associated with reproductive and nonreproductive complications, including obesity, insulin resistance and diabetes, dyslipidemia, and increased blood pressure. There is an urgent need for biomarkers that address both the reproductive and nonreproductive aspects of this complex syndrome. This review focuses on biomarkers, or potential ones, associated with the reproductive and nonreproductive aspects of PCOS, including anthropometric and clinical biomarkers, insulin and the insulin-like growth factor 1 system, lipids, anti-Müllerian hormone and gonadotropins, steroids, inflammatory and renal injury biomarkers, oxidative stress, and noncoding RNAs. We expect that this review will bring some light on the recent updates in the field and encourage researchers to join the exciting and promising field of PCOS biomarkers.