Media Releases

New study redefines how plaques grow in heart disease

August 12, 2013

TORONTO, ON — The growth of dead­ly plaque inside the walls of arter­ies may not hap­pen as sci­en­tists believed, research from the Uni­ver­si­ty of Toron­to and Mass­a­chu­setts Gen­er­al Hos­pi­tal has found.

The research also sug­gests a new poten­tial tar­get in the treat­ment of ath­er­o­scle­ro­sis, a lead­ing cause of car­dio­vas­cu­lar dis­ease and death glob­al­ly.

The research team found that macrophages, white blood cells that dri­ve ath­er­o­scle­ro­sis, repli­cate inside plaques. More­over, this growth is not reliant on cells out­side the plaques called mono­cytes, as sci­en­tists had assumed.

“Until now, the think­ing was that inflam­ma­to­ry macrophages arise main­ly from the recruit­ment of their pre­cur­sors — mono­cytes — from the blood­stream,” said Clint Rob­bins, lead author on the study and an Assis­tant Pro­fes­sor in U of T’s Depart­ments of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy, and Immunol­o­gy. “Our study shows that the accu­mu­la­tion of macrophages also depends on their pro­lif­er­a­tion local­ly with­in the devel­op­ing plaque.”

The jour­nal Nature Med­i­cine pub­lished the study results today.

The impact of the research on clin­i­cal treat­ments could be large. Many phar­ma­ceu­ti­cal com­pa­nies are pour­ing resources into poten­tial ther­a­pies that can block the recruit­ment of white blood cells into plaques. But if macrophages self-sus­tain through local cell divi­sion, block­ing recruit­ment may not be the best strat­e­gy.

“I think this work will force some major re-eval­u­a­tions,” said Fil­ip Swirs­ki, the study’s prin­ci­pal inves­ti­ga­tor who is a sci­en­tist in the Cen­ter for Sys­tems Biol­o­gy at Mass­a­chu­setts Gen­er­al Hos­pi­tal and an Assis­tant Pro­fes­sor at Har­vard Med­ical School. “Peo­ple have been think­ing of tar­get­ing mono­cyte influx to treat ath­er­o­scle­ro­sis, but they need to con­sid­er macrophage pro­lif­er­a­tion as an addi­tion­al or alter­na­tive approach, espe­cial­ly in estab­lished dis­ease.”

That approach might be bet­ter than tar­get­ing cir­cu­lat­ing mono­cytes, since inter­rupt­ing dis­ease-caus­ing process­es with­in plaques could spare oth­er ben­e­fi­cial immune respons­es that mono­cytes con­trol, said Swirs­ki.

As well, it could help improve the cur­rent stan­dard of care in treat­ing ath­er­o­scle­ro­sis: statin ther­a­py. Statins, in addi­tion to low­er­ing blood lipids that con­tribute to plaque, have anti-inflam­ma­to­ry prop­er­ties. The researchers are now look­ing at whether statins might lim­it the spread of macrophages with­in plaques.

“Addi­tion­al tar­get­ing of macrophage pro­lif­er­a­tion may fur­ther decrease inflam­ma­tion in ath­er­o­scle­ro­sis and prove clin­i­cal­ly advan­ta­geous,” said Rob­bins, who is also a sci­en­tist in the Toron­to Gen­er­al Research Insti­tute at Uni­ver­si­ty Health Net­work.

The researchers con­duct­ed their study in mice, and they cau­tion that much more research is need­ed to see how the work will trans­late to humans. But encour­ag­ing­ly, they found evi­dence of macrophage growth in plaques from human carotid arter­ies.

Next, the team will com­pare macrophage pro­lif­er­a­tion to mono­cyte recruit­ment dur­ing dif­fer­ent stages of ath­er­o­scle­ro­sis, and look at whether all macrophages, or only sub­sets, repli­cate.

The study was fund­ed by the U.S. Nation­al Insti­tutes of Health, the Mass­a­chu­setts Gen­er­al Hos­pi­tal, the Heart and Stroke Richard Lewar Cen­tre of Excel­lence in Car­dio­vas­cu­lar Research, and the Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy at the Uni­ver­si­ty of Toron­to.

This news release was part­ly adapt­ed from a Mass­a­chu­setts Gen­er­al Hos­pi­tal release by Sue McGreevey.


For more infor­ma­tion, con­tact:

Jim Old­field
Com­mu­ni­ca­tions Writer
Temer­ty Temer­ty Fac­ul­ty of Med­i­cine, Uni­ver­si­ty of Toron­to
Tel: 416–946-8423