Media Releases

U of T scientists redefine arterial wall inflammation, offering hope for cardiovascular disease treatment

December 7, 2015

TORONTO, ON — Researchers from the Uni­ver­si­ty of Toron­to have found that a spe­cif­ic cell type plays a key role in main­tain­ing healthy arter­ies after inflam­ma­tion. It’s a dis­cov­ery that could pro­vide treat­ment options for car­dio­vas­cu­lar dis­ease — one of the lead­ing caus­es of death in Cana­da.

The researchers found that a spe­cif­ic type of tis­sue macrophage, a group of white blood cells that defend against infec­tion, are cre­at­ed and oper­ate sep­a­rate­ly from oth­er macrophages that come from the bone mar­row.  Unlike bone mar­row macrophages, these cells live in the out­er lay­er of the arte­r­i­al wall, can self-repli­cate and help to heal the ves­sel after inflam­ma­tion.

“We’ve dis­cov­ered that a group of macrophages are cre­at­ed when the embryo is devel­op­ing, before the bone mar­row is func­tion­ing,” said Clin­ton Rob­bins, a pro­fes­sor in the Temer­ty Temer­ty Fac­ul­ty of Medicine’s Depart­ments of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy and Immunol­o­gy. “These macrophages can self-repli­cate and like­ly reg­u­late the nor­mal func­tion of our arter­ies. This is a fun­da­men­tal bio­log­i­cal dis­cov­ery that could play an impor­tant role in many car­dio­vas­cu­lar dis­eases.”

The jour­nal Nature Immunol­o­gy pub­lished the results of the study today.

Rob­bins and his team found that dur­ing infec­tion these self-repli­cat­ing macrophages leave the arte­r­i­al wall, while macrophages from the bone mar­row come in and engulf the bac­te­ria. The team thinks that once inflam­ma­tion resolves, the self-renew­ing macrophages return to heal the dam­aged tis­sue.

Using a spe­cial tag­ging sys­tem, they accu­rate­ly traced where the macrophages were com­ing from.

“Pre­vi­ous­ly, we couldn’t iden­ti­fy one macrophage from anoth­er because we were lim­it­ed by tech­nol­o­gy,” said Rob­bins, who is also the Peter Munk Chair of Aor­tic Dis­ease Research in the Toron­to Gen­er­al Research Insti­tute at Uni­ver­si­ty Health Net­work. “Now we can see exact­ly where they’re com­ing from and where they’re going. Our job now is to get a bet­ter under­stand­ing of what these dif­fer­ent macrophage pop­u­la­tions are doing.”

Next, the researchers will study how these res­i­dent macrophages inter­act with their tis­sue envi­ron­ment and exact­ly what role they might play in car­dio­vas­cu­lar dis­ease. By under­stand­ing the rela­tion­ship between the dif­fer­ent cell types, they hope to tar­get inflam­ma­tion caused by infec­tion or ath­er­o­scle­ro­sis more effec­tive­ly.

“We know that while bone mar­row macrophages remove bac­te­ria, they can also cause ath­er­o­scle­ro­sis by enter­ing the arte­r­i­al wall and mul­ti­ply­ing,” said Rick­vin­der Besla, grad­u­ate stu­dent and co-lead author. “In the old mod­el, you might try to shut the bone mar­row response down, but this leaves the patient immuno­sup­pressed. Our new mod­el sug­gests we could pos­si­bly reduce inflam­ma­tion by boost­ing the activ­i­ty of these self-repli­cat­ing macrophages.”

Rob­bins acknowl­edges that there’s still a lot to learn about the com­plex­i­ty of these macrophages and how they inter­act with their envi­ron­ment and oth­er cells.

“Arter­ies are more than tubes that shut­tle blood around. They cre­ate a com­plex and dynam­ic net­work that reacts to inflam­ma­tion and dis­ease in dif­fer­ent ways. We’re excit­ed to fig­ure out anoth­er piece of this puz­zle and how we might tar­get car­dio­vas­cu­lar dis­ease in the future.”


ABOUT UNIVERSITY OF TORONTO Temer­ty Temer­ty Fac­ul­ty of Med­i­cine:
The Uni­ver­si­ty of Toron­to is at the heart of one of the great bio­med­ical research, edu­ca­tion and clin­i­cal care net­works in the world. With nine ful­ly affil­i­at­ed hos­pi­tals and research insti­tutes and 20 com­mu­ni­ty-affil­i­at­ed hos­pi­tals and clin­i­cal care sites, the Uni­ver­si­ty of Toron­to is a research pow­er­house that offers unpar­al­leled oppor­tu­ni­ties for its 6,800 fac­ul­ty and 7,000-plus stu­dents at all lev­els. Near­ly half of Ontario’s med­ical doc­tors and 25 per cent of all health and bio­med­ical PhDs in Cana­da were trained at the Uni­ver­si­ty of Toron­to, which con­sis­tent­ly ranks among the top uni­ver­si­ties world­wide.

The Peter Munk Car­diac Cen­tre is the pre­mier car­diac cen­tre in Cana­da. Since it opened in 1997, the Cen­tre has saved and improved the lives of car­diac and vas­cu­lar patients from around the world. Each year, approx­i­mate­ly 55,000 patients receive inno­v­a­tive and com­pas­sion­ate care from mul­ti­dis­ci­pli­nary teams in the Peter Munk Car­diac Cen­tre, and the Cen­tre trains more car­di­ol­o­gists, car­dio­vas­cu­lar sur­geons and vas­cu­lar sur­geons than any oth­er hos­pi­tal in Cana­da. The Cen­tre is based at the Toron­to Gen­er­al Hos­pi­tal and the Toron­to West­ern Hos­pi­tal — mem­bers of Uni­ver­si­ty Health Net­

Hei­di Singer
Media Rela­tions Spe­cial­ist
Temer­ty Temer­ty Fac­ul­ty of Med­i­cine, Uni­ver­si­ty of Toron­to
Tel: 416–978-5811