Arterial and aortic valve calcification inversely correlates with osteoporotic bone remodelling: a role for inflammation.
OBJECTIVE
Westernized countries face a growing burden of cardiovascular calcification and osteoporosis. Despite its vast clinical significance, the precise nature of this reciprocal relationship remains obscure. We hypothesize that cardiovascular calcification progresses with inflammation and inversely correlates with bone tissue mineral density (TMD).


RESULTS
Arterial, valvular, and bone metabolism were visualized using near-infrared fluorescence (NIRF) molecular imaging agents, targeting macrophages and osteogenesis. We detected significant arterial and aortic valve calcification in apoE(-/-) mice with or without chronic renal disease (CRD, 30 weeks old; n = 28), correlating with the severity of atherosclerosis. We demonstrated decreases in osteogenic activity in the femurs of apoE(-/-) mice when compared with WT mice, which was further reduced with CRD. Three-dimensional micro-computed tomography imaging of the cortical and cancellous regions of femurs quantified structural remodelling and reductions in TMD in apoE(-/-) and CRD apoE(-/-) mice. We established significant correlations between arterial and valvular calcification and loss of TMD (R(2) = 0.67 and 0.71, respectively). Finally, we performed macrophage-targeted molecular imaging to explore a link between inflammation and osteoporosis in vivo. Although macrophage burden, visualized as uptake of NIRF-conjugated iron nanoparticles, was directly related to the degree of arterial and valvular inflammation and calcification, the same method inversely correlated inflammation with TMD (R(2) = 0.73; 0.83; 0.75, respectively).


CONCLUSIONS
This study provides direct in vivo evidence that in arteries and aortic valves, macrophage burden and calcification associate with each other, whereas inflammation inversely correlates with bone mineralization. Thus, understanding inflammatory signalling mechanisms may offer insight into selective abrogation of divergent calcific phenomena.
Hjortnaes
Jesper
J
Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, MA, USA.
Butcher
Jonathan
J
Figueiredo
Jose-Luiz
JL
Riccio
Mark
M
Kohler
Rainer H
RH
Kozloff
Kenneth M
KM
Weissleder
Ralph
R
Aikawa
Elena
E
D000818:Animals; D001024:Aortic Valve Stenosis / Q000209:etiology* / Q000503:physiopathology; D050197:Atherosclerosis / Q000503:physiopathology*; D015519:Bone Density / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D002114:Calcinosis / Q000209:etiology* / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000503:physiopathology; D002908:Chronic Disease; D005269:Femur; D007249:Inflammation / Q000150:complications; D007674:Kidney Diseases / Q000503:physiopathology; D051379:Mice; D010024:Osteoporosis / Q000503:physiopathology*