Mitochondrial damage-associated molecular patterns and vascular function

Abstract

Immune system activation occurs not only due to foreign stimuli, but also due to endogenous molecules. As such, endogenous molecules that are released into the circulation due to cell death and/or injury alarm the immune system that something has disturbed homeostasis and a response is needed. Collectively, these molecules are known as damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs (mtDAMPs) are potent immunological activators due to the bacterial ancestry of mitochondria. Mitochondrial DAMPs are recognized by specific pattern recognition receptors of the innate immune system, some of which are expressed in the cardiovascular system. Cell death leads to release of mtDAMPs that may induce vascular changes by mechanisms that are currently not well understood. This review will focus on recently published evidence linking mtDAMPs and immune system activation to vascular dysfunction and cardiovascular disease.

Obesity, reproduction and oxidative stress

“…Длительное и постоянное воздействие свободных радикалов сопро-вождается массовым повреждением молекул. Это приво-дит к активации программированной клеточной гибели, в плазме нарастает количество фрагментов митохон-дрий, которые являются индукторами системного вос-палительного ответа [47]. Повреждение клеток приводит к высокой продукции цитокинов, которые генерируют дополнительные активные формы кислорода и увеличи-вают скорость пероксидации липидов [48].…”

“…Учитывая наличие корреляции между маркерами окси-дативного стресса, антиоксидантного статуса и метабо-лического синдрома, некоторые ученые предполагают, что оксидативный стресс является ранним маркером метаболического синдрома и играет центральную роль в его патогенезе [49]. Доказана роль оксидативного стресса в развитии эндотелиальной дисфункции [50]. Таким образом, оксидативный стресс является одним из звеньев формирования патогенетических измене-ний в организме [51].…”

Nucleic Acid Delivery for Endothelial Dysfunction in Cardiovascular Diseases

“…28 Thus, impaired organelles act as potential triggers (presenting endothelial DAMPs) that generate excessive reactive oxygen species (ROS), which can increase the expression of endothelial adhesion molecules and inflammatory cytokines. 29 To varying degrees, the activation of the endothelium may be offset by the endothelial elaboration of anti-inflammatory cytokines such as IL-10. 30 It is the shift in balance between the secreted proinflammatory and anti-inflammatory cytokines that modulates the inflammatory cascade associated with dysfunctional endothelium.…”

“…32 Interestingly, mitochondrial DNA (mtDNA), in circulation as well as in the cellular cytosol, induces genomic DNA damage and subsequent endothelial dysfunction, which is implicated in a host of vascular diseases like diabetes, hypertension, and atherosclerosis. 29 Endothelial mitochondria are endowed with significant DNA repair capacity. However, mitochondrial proximity with the oxidative respiratory chain and the absence of histone or chromatin structures around the mitochondria render it susceptible to oxidative damage, making it a potential presenter of DAMPs and a source of endothelial dysfunction.…”

11th International Symposium on Mechanisms of Vasodilation October 4-6, 2013, University Hospital Zurich, Switzerland

“…4), by Clinton R. Webb from Augusta, USA, who gave a talk on "Mitrochondria-derived peptides: novel mediators of vasodilation" [21]. Dr Bohr was one of the pioneers who investigated the function of vascular smooth muscle cells, and, in particlar, established the key role of changes in intracellular Ca 2+ concentration in their relaxation and contraction.…”