Found 4 results
Review
02 December 2024The Interplay of Heart Failure and Lung Disease: Clinical Correlations, Mechanisms, and Therapeutic Implications
Heart failure (HF) is a common clinical syndrome marked by reduced cardiac output, elevated intracardiac pressures, and heart dysfunction. Chronic HF (CHF) is a syndrome characterized by a lack of blood flow and impaired pumping ability to the heart over time, while acute HF (AHF) arises suddenly due to incidents like myocardial infarction or cardiac arrest. HF has a significant impact on pulmonary health and function, leading to conditions such as pulmonary edema and restrictive lung patterns. Clinical evidence highlights the bidirectional relationship between HF and lung dysfunction. Declining lung function serves as a predictor for HF progression and severity, while HF contributes to worsening lung health. Animal models that induce HF through surgical methods further demonstrate the connection between heart and lung pathology. The main mechanisms linking HF and lung dysfunction are pressure overload and chronic systemic inflammation, with changes in the extracellular matrix (ECM) also playing a role. Additionally, environmental factors like air pollution exacerbate lung inflammation, increasing the risk of both HF and chronic obstructive pulmonary disease (COPD) incidence. Combined treatment approaches involving pharmaceutical drugs such as statins, Angiotensin-converting enzyme (ACE) inhibitors, and Angiotensin receptor blockers (ARBs) may benefit by reducing inflammation. This review will explore the complex interplay between HF and lung function, emphasizing their interconnected pathophysiology and potential integrated treatment strategies.
Review
15 November 2024Ion Channels in the Immune Response of Asthma
Asthma is a common respiratory disorder characterized by chronic inflammation of the lower airways, contributing to significant morbidity, mortality, and a substantial global economic burden. It is now understood as a heterogeneous condition, with ongoing research shedding light on its complex immunological underpinnings. Ion channels, which are specialized transmembrane proteins that facilitate ion movement based on electrochemical gradients, play a crucial role in the pathophysiology of asthma. Ion channels regulate essential processes like maintaining epithelial hydroelectrolyte balance and also play a role in modulating immune responses involved in asthma. We discuss the connection between ion channel activity and immune regulation in asthma, focusing on ion channel regulation of immune cell behavior, airway hyperresponsiveness, and inflammation in asthma. Understanding ion channels in asthma could lead to the development of targeted therapies modulating their activity, thereby enhancing disease management and patient outcomes.
Article
31 March 2024
The Asthma Risk Gene, GSDMB, Promotes Mitochondrial DNA-induced ISGs Expression
Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent ISGs induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. GSDMB is significantly associated with RANTES expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of GSDMB promotes DNA-induced IFN and ISGs expression in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of GSDMB led to weakened induction of interferon (IFNs) and ISGs in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocalization of STING to Golgi, leading to the phosphorylation of IRF3 and induction of IFNs and ISGs. mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of ISGs.
Meeting Report
20 February 2024The Cellular and Metabolic Bases of Organ Fibrosis: UNIA Workshop 2023 in Baeza, Spain
Fibrosis is defined by scarring and tissue hardening caused by excess deposition of extracellular matrix components, mainly collagens. A fibrotic response can occur in any tissue of the body and is the final outcome of an unbalanced reaction to inflammation and wound healing induced by a variety of insults, including persistent infections, autoimmune reactions, allergic responses, chemical exposure, radiation, and tissue injury. The accumulation of extracellular matrix proteins replaces the living tissue and disrupts the architecture leading to organ malfunction. Fibrosis remains a major clinical and therapeutic challenge and has been estimated to account for 45% of deaths in the developed world. While major advances regarding mechanistic knowledge on the underlying cell biology alterations in fibrosis have helped to characterize the main phases and mediators involved, this knowledge has not yielded significant progress in treatment. Only recently, the metabolic features associated to fibrosis have begun to emerge. This information, likely representing only the tip of the iceberg, suggests that metabolic derangement is a key culprit in the pathophysiology of fibrogenesis. The Workshop on The Cellular and Metabolic Bases of Organ Fibrosis, International University of Andalusia, Baeza, Spain, October 8–11, 2023 aimed to discuss the current knowledge and novel perspectives on the mechanisms contributing to the development of fibrosis in different organs and tissues, with particular focus on new methodological developments in metabolomics and therapeutic strategies.
