Inflammation Mediates Adipose Derived Stem Cell Dysfunction in Hypertension

Abstract

Adipose tissue secretes inflammation cytokines and is vital for obesity‐induced chronic inflammation caused by infiltrated macrophages. Emerging evidence implicate inflammation in obesity and hypertension (HTN), two major modifiable risk factors for cardiovascular disease. However, not all obesity patients develop HTN; the role of adipose stem cells (ASCs) in obesity‐associated HTN has not been investigated and led us to hypothesize that ASCs from obese‐HTN (OH) patients express increased inflammatory cytokines and oxidative stress, leading to diminished reparative capacity. ASCs were isolated from 12 human subjects [6 OH; 6 obese‐normal (ON)] and 8 rats [4 normotensive Wistar Kyoto (WKY) rats; 4 spontaneously hypertensive rats (SHR)]. ASCs from OH subjects have 12 fold higher TNF‐α level, 30% increase in reactive oxygen species (ROS) and 20% in proliferation than ON subjects. ASCs from SHR exhibited higher inflammatory cytokine, ROS, and proliferation than ASCs from WKY. To determine therapeutic effects of ASCs for HTN, one bolus of 5 million ASCs from WKY rats was intravenously injected into SHR and blood pressure (BP) was monitored for 3 weeks. We observed a 17mmHg decrease in systolic BP one week following cell administration. Systolic BP gradually increased to levels of SHR control. OH is associated with elevated inflammatory status in ASCs. ASCs from WKY possess transient therapeutic effects against HTN. Data suggest that anti‐inflammation treatment and multiple injections of ASCs may be employed for persistent anti‐HTN effect. Thus, inflammation status of ASCs may be a useful predictor for OH.