"But that didn't explain obesity's connection to high levels of CRP and it also was not clear why CRP is higher in patients who have metabolic disorders," Yeh said.
So the research team decided to see whether fat cells themselves can be stimulated by inflammatory cytokines or resistin to produce CRP. To help find out, plastic surgery patients at M. D. Anderson donated adipose tissue that would have been discarded, and the research team then isolated fat cells, cultured them and stimulated them under a number of different conditions. They found the cells produced cytokines that resulted in inflammation and that this process triggered production of high levels of C-reactive proteins.
The researchers also discovered that resistin, the hormone associated with diabetes and insulin resistance, can stimulate production of CRP proteins. "And this is interesting because it is known that resistin is itself produced by fat cells," Yeh said.
"We know that patients with metabolic syndromes have higher levels of CRPs, as well as a higher risk of developing heart disease and stroke, but no one understands why that is," Yeh said. "If fat cells by themselves produce inflammatory signals that trigger cells to produce CRPs, and if CRPs also produce biological effects on vascular walls, that could explain the higher risk of cardiovascular disease."
The investigators then solved the other part of the puzzle why it is that aspirin, statin drugs and an agent known as troglitazone, used to treat diabetes, can reduce CRP levels. They exposed the cultured fat cells that were producing high levels of CRPs to these drugs, and found production of the proteins declined. "We knew from studying patients that these drugs can reduce C-reactive proteins, but now we have direct proof of their benefit."
Even as the CRP picture becomes clearer, there is still much that i
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16-Sep-2005