Convergent Sets of Data from In Vivo and In Vitro Methods Point to an Active Role of Hsp60 in Chronic Obstructive Pulmonary Disease Pathogenesis

BACKGROUND: It is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses. METHODS AND RESULTS: Bronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between the number of neutrophils and Hsp60 levels. Double-immunostaining showed that Hsp60-positive neutrophils were significantly increased in COPD patients. We then investigated in vitro the effect on Hsp60 expression in bronchial epithelial cells (16HBE) caused by oxidative stress, a hallmark of COPD mucosa, which we induced with H\u2082O\u2082. This stressor determined increased levels of Hsp60 through a gene up-regulation mechanism involving NFkB-p65. Release of Hsp60 in the extracellular medium by the bronchial epithelial cells was also increased after H\u2082O\u2082 treatment in the absence of cell death. CONCLUSIONS: This is the first report clearly pointing to participation of Hsps, particularly Hsp60, in COPD pathogenesis. Hsp60 induction by NFkB-p65 and its release by epithelial cells after oxidative stress can have a role in maintaining inflammation, e.g., by stimulating neutrophils activity. The data open new scenarios that might help in designing efficacious anti-inflammatory therapies centered on Hsp60 and applicable to COP

Cardiopulmonary Exercise Performance and Endothelial Function in Convalescent COVID-19 Patients

Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors

Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities

Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a Potential Therapeutic Target

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting

Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease

Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons

NFkB-p65 binding sites in the human <i>hsp60</i> gene.

<p>NFkB-p65 binding sites in the human <i>hsp60</i> gene.</p