Cardiovascular disease and the role of oral bacteria

In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD

A comparative study of the self-immolation of para-aminobenzylalcohol and hemithioaminal-based linkers in the context of protease-sensitive fluorogenic probes.

International audienceThis study focuses on the disassembly-behavior of self-immolative pro-fluorescent linkers under physiological conditions and through an enzyme-initiated domino reaction. The targeted linkers are based on para-aminobenzylalcohol (PABA) or hemithioaminal derivatives of para-carboxybenzaldehyde or glyoxilic acid. We found that a fine tuning of the kinetic properties could be obtained through the modulation of the linker structure, giving either a fast signal response or free-adaptable systems suitable for the design of protease-sensitive fluorogenic probes or prodrug systems

In Vitro and Ex Vivo Evaluation of Smart Infra-Red Fluorescent Caspase-3 Probes for Molecular Imaging of Cardiovascular Apoptosis

International audiencePURPOSE:The aim of this paper is to develop new optical bioprobes for the imaging of apoptosis.PROCEDURE:We developed quenched near-infrared probes which become fluorescent upon cleavage by caspase-3, the key regulatory enzyme of apoptosis.RESULTS:Probes were shown to be selectively cleaved by recombinant caspase-3. Apoptosis of cultured endothelial cells was associated with an increased fluorescent signal for the cleaved probes, which colocalized with caspase-3 and was reduced by the addition of a caspase-3 inhibitor. Flow cytometry demonstrated a similar profile between the cleaved probes and annexin V. Ex vivo experiments showed that sections of hearts obtained from mice treated with the proapoptotic drug doxorubicin displayed an increase in the fluorescent signal for the cleaved probes, which was reduced by a caspase-3 inhibitor.CONCLUSION:We demonstrated the capacity of these novel probes to detect apoptosis by optical imaging in vitro and ex vivo

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis

International audienceApoptosis is a regulated process, leading to cell death, which is involved in several pathologies including neurodegenerative diseases and stroke. Caspase-3 is a key enzyme of the apoptotic pathway and is considered as a major target for the treatment of abnormal cell death. Sensitive and non-invasive methods to monitor caspase-3 activity in cells and in the brain of living animals are needed to test the efficiency of novel therapeutic strategies. In the present study, we have biochemically characterized a caspase-3 far-red fluorescent probe, QCASP3.2, that can be used to detect apoptosis in vivo. The specificity of cleavage of QCASP3.2 was demonstrated using recombinant caspases and protease inhibitors. The functionality of the probe was also established in cere-bellar neurons cultured in apoptotic conditions. QCASP3.2 did not exhibit any toxicity and appeared to accurately reflect the induction and inhibition of caspase activity by H 2 O 2 and PACAP, respectively, both in cell lysates and in cultured neurons. Finally, intravenous injection of the probe after cere-bral ischemia revealed activation of caspase-3 in the infarcted hemisphere. Thus, the present study demonstrates that QCASP3.2 is a suitable probe to monitor apoptosis both in vitro and in vivo and illustrates some of the possible applications of this caspase-3 fluorescent probe