Nanodomains in cardiopulmonary disorders and the impact of air pollution

Abstract

Air pollution is a major environmental threat and each year about 7 million people reported to die as a result of air pollution. Consequently, exposure to air pollution is linked to increased morbidity and mortality world-wide. Diesel automotive engines are a major source of urban air pollution in the western societies encompassing particulate matter and diesel exhaust particles (DEP). Air pollution is envisioned as primary cause for cardiovascular dysfunction, such as ischemic heart disease, cardiac dysrhythmias, heart failure, cerebrovascular disease and stroke. Air pollution also causes lung dysfunction, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and specifically exacerbations of these diseases. DEP induces inflammation and reactive oxygen species production ultimately leading to mitochondrial dysfunction. DEP impair structural cell function and initiate the epithelial-to-mesenchymal transition, a process leading to dysfunction in endothelial as well as epithelial barrier, hamper tissue repair and eventually leading to fibrosis. Targeting cyclic adenosine monophosphate (cAMP) has been implicated to alleviate cardiopulmonary dysfunction, even more intriguingly cAMP seems to emerge as a potent regulator of mitochondrial metabolism. We propose that targeting of the mitochondrial cAMP nanodomain bear the therapeutic potential to diminish air pollutant — particularly DEP — induced decline in cardiopulmonary function.

Elevated cAMP Protects against Diclofenac-Induced Toxicity in Primary Rat Hepatocytes: A Protective Effect Mediated by the Exchange Protein Directly Activated by cAMP/cAMP-Regulated Guanine Nucleotide Exchange Factors

“…cAMP is spatially and temporally regulated, with physiologically relevant signals being those constrained in nano-domains, thereby allowing for distinct responses to be propagated within the cell -this is known as compartmentalization of cAMP. Compartmentalization of cAMP by synthesis via ACs, by degradation by PDEs and targeting of cAMP effector proteins by Akinase anchoring proteins (AKAPs), are thought to profoundly affect the net-outcome of cAMP effects (Monterisi et al, 2017;Zuo et al, 2019;Cattani-Cavalieri, Valença and Schmidt, 2020;Ercu et al, 2020). In this regard, cAMP elevation has the potential to regulate both pro-apoptotic and anti-apoptotic signals (Insel et al, 2012).…”

“…Sub-cellular cAMP's existence could explain the opposing effect of forskolin and IBMX results compartmentalized signaling (Monterisi et al, 2017;Zuo et al, 2019;Cattani-Cavalieri, Valença and Schmidt, 2020). For example, the mitochondrial matrix has been identified as containing a unique cellular cAMP compartment where sACs regulate cAMP and thus mitochondria function independently of the cytoplasm (Jakobsen, Lange and Bak, 2019) ( Figure 10).…”

An Exploratory Study of the Relationships Between Diesel Engine Exhaust Particle Inhalation, Pulmonary Inflammation and Anxious Behavior

“…Based on these disadvantages, heavy casualties may occur. In the long term, lifetime DEP inhalation from air pollution may cause significant pathological alterations, such as asthma [29,30], allergic reactions [31], and cardiac pressures [32]. Moreover, DEP exposure to neuronal cells elevates neuronal oxidative stress and inflammation [33], as well as neurotoxicity [34].…”

Differences in disease prevalence among homeless and non-homeless veterans at an urban VA hospital

“…33,34 This population may also tend to spend more time outside increasing exposure to environmental air pollutants and particulate matter that is associated with COPD and other chronic lung diseases. 35,36 We did not assess environmental risk factors in our study, but providers should consider the incorporation of environmental assessments with appropriate referrals as part of their plans for managing chronic respiratory conditions in homeless individuals.…”