A growing number of extreme climate events are occurring in the setting of ongoing climate change, with an increase in both the intensity and frequency. It has been shown that ambient temperature challenges have a direct and highly varied impact on cardiovascular health. With a rapidly growing amount of literature on this issue, we aim to review the recent publications regarding the impact of cold and heat on human populations with regard to cardiovascular disease (CVD) mortality/morbidity while also examining lag effects, vulnerable subgroups, and relevant mechanisms. Although the relative risk of morbidity/mortality associated with extreme temperature varied greatly across different studies, both cold and hot temperatures were associated with a positive mean excess of cardiovascular deaths or hospital admissions. Cause-specific study of CVD morbidity/mortality indicated that the sensitivity to temperature was disease-specific, with different patterns for acute and chronic ischemic heart disease. Vulnerability to temperature-related mortality was associated with some characteristics of the populations, including sex, age, location, socioeconomic condition, and comorbidities such as cardiac diseases, kidney diseases, diabetes, and hypertension. Temperature-induced damage is thought to be related to enhanced sympathetic reactivity followed by activation of the sympathetic nervous system, renin-angiotensin system, as well as dehydration and a systemic inflammatory response. Future research should focus on multidisciplinary adaptation strategies that incorporate epidemiology, climatology, indoor/building environments, energy usage, labor legislative perfection, and human thermal comfort models. Studies on the underlying mechanism by which temperature challenge induces pathophysiological response and CVD await profound and lasting investigation.

Objective— To evaluate the role of early-life exposure to airborne fine particulate matter (diameter, <2.5 μm [PM _2.5 ]) pollution on metabolic parameters, inflammation, and adiposity; and to investigate the involvement of oxidative stress pathways in the development of metabolic abnormalities. Methods and Results— PM _2.5 inhalation exposure (6 h/d, 5 d/wk) was performed in C57BL/6 mice (wild type) and mice deficient in the cytosolic subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47 ^phox (p47 ^phox−/− ) beginning at the age of 3 weeks for a duration of 10 weeks. Both groups were simultaneously fed a normal diet or a high-fat diet for 10 weeks. PM _2.5 -exposed C57BL/6 mice fed a normal diet exhibited metabolic abnormalities after exposure to PM _2.5 or FA for 10 weeks. Consistent with insulin resistance, these abnormalities included enlarged subcutaneous and visceral fat contents, increased macrophage infiltration in visceral adipose tissue, and vascular dysfunction. Ex vivo–labeled and infused monocytes demonstrated increased adherence in the microcirculation of normal diet– or high-fat diet–fed PM _2.5 -exposed mice. p47 ^phox−/− mice exhibited an improvement in parameters of insulin resistance, vascular function, and visceral inflammation in response to PM _2.5 . Conclusion— Early-life exposure to high levels of PM _2.5 is a risk factor for subsequent development of insulin resistance, adiposity, and inflammation. Reactive oxygen species generation by NADPH oxidase appears to mediate this risk.

We have previously shown that chronic exposure to ambient fine particulate matter (less than 2.5 μm in aerodynamic diameter, PM_2.5) pollution in conjunction with high-fat diet induces insulin resistance through alterations in inflammatory pathways. In this study, we evaluated the effects of PM_2.5 exposure over a substantive duration of a rodent’s lifespan and focused on the impact of long-term exposure on adipose structure and function. C57BL/6 mice were exposed to PM_2.5 or filtered air (FA) (6 h/day, 5 days/week) for duration of 10 months in Columbus, OH. At the end of the exposure, PM_2.5-exposed mice demonstrated insulin resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed group. Although there were no significant differences in circulating cytokines between PM_2.5- and FA-exposed groups, circulating adiponectin and leptin were significantly decreased in PM_2.5-exposed group. PM_2.5 exposure also led to inflammatory response and oxidative stress as evidenced by increase of Nrf2-regulated antioxidant genes. Additionally, PM_2.5 exposure decreased mitochondrial count in visceral adipose and mitochondrial size in interscapular adipose depots, which were associated with reduction of uncoupling protein 1 (UCP1) expression and downregulation of brown adipocyte-specific gene profiles. These findings suggest that long-term ambient PM_2.5 exposure induces impaired glucose tolerance, IR, inflammation, and mitochondrial alteration, and thus, it is a risk factor for the development of type 2 diabetes.

Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases. However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells. Inhalation exposure of the mice to environmentally relevant fine particulate matter (aerodynamic diameter < 2.5 μm, PM_2.5) induces endoplasmic reticulum (ER) stress and activation of unfolded protein response (UPR) in the lung and liver tissues as well as in the mouse macrophage cell line RAW264.7. Ambient PM_2.5 exposure activates double-strand RNA-activated protein kinase-like ER kinase (PERK), leading to phosphorylation of translation initiation factor eIF2α and induction of C/EBP homologous transcription factor CHOP/GADD153. Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for PM_2.5-induced apoptosis. Furthermore, PM_2.5 exposure can activate ER stress sensor IRE1α, but it decreases the activity of IRE1α in splicing the mRNA encoding the UPR trans-activator X-box binding protein 1 (XBP1). Together, our study suggests that PM_2.5 exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2α-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient PM_2.5 exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis.

Background: Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods: Male ApoE knockout (ApoE^-/-) mice inhaled concentrated fine ambient PM (PM < 2.5 μm in aerodynamic diameter; PM_2.5) or filtered air (FA) for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM_2.5 exposure in different adipose depots of ApoE^-/- mice to understand responses to chronic inhalational stimuli. Results: Exposure to PM_2.5 induced an increase in the production of reactive oxygen species (ROS) in brown adipose depots. Additionally, exposure to PM_2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT) and brown adipose tissues (BAT), while mitochondrial size was also reduced in BAT. In BAT, PM_2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions: PM_2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM_2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.