dimanche 15 mai 2016

Heartburn drugs are associated with higher cardiac risk: why?



"The salient findings of this study are that long-term exposure to proton pump inhibition: 1) impairs lysosomal acidification and enzyme activity, in association with protein aggregate accumulation; 2) increases the generation of reactive oxygen species, and impairs the NO synthase pathway; 3) accelerates telomere erosion in association with reduced expression of the shelterin complex; and 4) speeds endothelial aging as manifested by impaired cell proliferation and angiogenesis, together with histological markers of senescence and endothelial-to-mesenchyme transition. Our results in primary human EC are consistent with the recent finding that PPIs impair the activity of lysosomal enzymes in several immortalized cell lines including A549, Caco2, HEK293, and HepG2.15 Lysosomes bind to autophagosomes to complete the process of autophagy,29 which comprises the degradation and elimination of unwanted cellular products including misfolded proteins.14, 15 An impairment of lysosomal acidification and reduced lysosomal enzyme activity might be expected to result in an accumulation of protein aggregates."

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