Hemostasis, endothelial stress, inflammation, and the metabolic syndrome

Abstract

Obesity and the metabolic syndrome (MS) are two of the pressing healthcare problems of our time. The MS is defined as increased abdominal obesity in concert with elevated fasting glucose levels, insulin resistance, elevated blood pressure, and plasma lipids. It is a key risk factor for type 2 diabetes mellitus (T2DM) and for cardiovascular complications and mortality. Here, we review work demonstrating that various aspects of coagulation and hemostasis, as well as vascular reactivity and function, become impaired progressively during chronic ingestion of a western diet, but also acutely after meals. We outline that both T2DM and cardiovascular disease should be viewed as inflammatory diseases and describe that chronic overload of free fatty acids and glucose can trigger inflammatory pathways directly or via increased production of ROS. We propose that since endothelial stress and increases in platelet activity precede inflammation and overt symptoms of the MS, they are likely the first hit. This suggests that endothelial activation and insulin resistance are probably causative in the observed chronic low-level metabolic inflammation, and thus both metabolic and cardiovascular complications linked to consumption of a western diet.

Leisure-Time Physical Activity, Sedentary Behaviour and Diet Quality are Associated with Metabolic Syndrome Severity: The PREDIMED-Plus Study

“…In addition, pro-inflammatory diets are associated with an increased risk of MetS [45]. Our results also agree these previous findings, as well as that a pro-inflammatory state is one component of MetS [46].…”

Peri‐prostatic adipose tissue: the metabolic microenvironment of prostate cancer

“…At least some of these factors may also be produced by infiltrating immune cells such as macrophages. Strikingly, ~30% of the 100 most significantly expressed genes in adipose tissues that are correlated with body mass encode inflammation‐related genes ; however, the interaction between inflammatory markers, insulin resistance, obesity and metabolic syndrome is complex and the current lack of detailed metabolic phenotyping of patients with PCa makes it challenging to determine the extent to which PPAT inflammation is a consequence of obesity or metabolic syndrome.…”

Hypertriglyceridemia is associated with platelet hyperactivation in metabolic syndrome patients

“…As we know, platelet activation is known to be associated with atherogenesis and cardiovascular morbidity 21 . In MetS patients, platelet hyperreactivity may be the result of insulin resistance, inflammation and oxidative stress 2‐4,7,22 . In addition, their PFA‐100 CT was significantly shorter than that of the non‐MetS group, who have one or two risk factors (106 s vs 113 s, P < .05), while there was no difference between the NC group and non‐MetS group, indicating that MetS as an independent disease has distinct haemostatic character.…”

“…Long‐term, MetS individuals tend to develop atherosclerotic plaque as a chronic inflammatory process characterised by increased levels of inflammatory markers, such as tumour necrosis factor, interleukin‐6, leptin, angiotensin II and plasminogen activator factor 1, all of whom are capital prothrombotic factors 5,6 . Besides increased inflammatory markers, the prothrombotic state in MetS is mainly caused by endothelial dysfunction and platelet hyperactivity 7 …”