COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series)

PulmCirc 2018 Jan-Mar;8(1):2045894018758528. doi: 10.1177/2045894018758528.

COPD as an endothelial disorder: endothelial injury linking lesions in the lungs and other organs? (2017 Grover Conference Series).

Polverino F1,2, Celli BR1,2,  Owen CA1,2.

Author information

1
1 Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
2
2 Lovelace Respiratory Research Institute, Albuquerque, NM, USA.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by chronic expiratory airflow obstruction that is not fully reversible. COPD patients develop varying degrees of emphysema, small and large airway disease, and various co-morbidities. It has not been clear whether these co-morbidities share common underlying pathogenic processes with the pulmonary lesions. Early research into the pathogenesis of COPD focused on the contributions of injury to the extracellular matrix and pulmonary epithelial cells. More recently, cigarette smoke-induced endothelial dysfunction /injury have been linked to the pulmonary lesions in COPD (especially emphysema) and systemic co-morbidities including atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we review the evidence linking endothelial injury to COPD, and the pathways underlying endothelial injury and the “vascular COPD phenotype” including: (1) direct toxic effects of cigarette smoke on endothelial cells; (2) generation of auto-antibodies directed against endothelial  cells; (3) vascular inflammation; (4) increased oxidative stress levels in vessels inducing increases in lipid peroxidation and increased activation of the receptor for advanced glycation end-products (RAGE); (5) reduced activation of the anti-oxidant pathways in endothelial cells; (6) increased endothelial cell release of mediators with vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and reduced endothelial cell expression of mediators that promote vasodilation and homeostasis of endothelial  cells (nitric oxide synthase and prostacyclin); and (7) increased endoplasmic reticular stress and the unfolded protein response in endothelial cells. We also review the literature on studies of drugs that inhibit RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), or vasodilators developed for idiopathic pulmonary arterial hypertension that have been tested on cell culture systems, animal models of COPD, and/or smokers and COPD patients.

KEYWORDS:

RAGE; apoptosis; oxidative stress; pulmonary endothelium; renal injury

 2018 Mar;109:1-5. doi: 10.1016/j.maturitas.2017.12.001. Epub 2017 Dec 6.

The link between depression and atherosclerosis through the pathways of inflammation and endothelium dysfunction.

Chrysohoou C1, Kollia N2, Tousoulis D3.

Author information

1
First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece. Electronic address: chrysohoou@usa.net.
2
Department of Nutrition & Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
3
First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece.

Abstract

A large body of evidence suggests that depression increases the risk of cardiovascular morbidity and mortality. The elevated risk associated with depression is not limited to clinical major depressive disorder but also extends to sub-syndromal depressive symptoms and constructs with overlapping characteristics, such as vital exhaustion. Multiple pathophysiological pathways are involved in the relationship between depressive symptoms and atherosclerosis and its clinical manifestations and progression. These underlying mechanisms are not yet fully understood and need further clarification. This review examines inflammation and endothelium dysfunction  as potential biological factors involved in the relationship between depressive symptoms and atherosclerosis. It has been reported that systemic inflammation and psychological factors interact through complex pathophysiological and behavioral mechanisms and one question that has been raised concerns whether the inflammation drives depression or vice versa, or whether the association is merely coincidental. Although further investigation is needed, including well-designed prospective studies, to address this question thoroughly, it seems that there is a feedback relationship, although the biological pathways of each direction may be distinct.

KEYWORDS:

Cardiovascular disease; Depression; Mechanisms

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