Current and novel radiopharmaceuticals for imaging cardiovascular inflammation.

Cardiovascular disease (CVD) remains the leading cause of death worldwide despite advances in diagnostic technologies and treatment strategies. The underlying cause of most CVD is atherosclerosis, a chronic disease driven by inflammatory reactions. Atherosclerotic plaque rupture could cause arterial occlusion leading to ischemic tissue injuries such as myocardial infarction (MI) and stroke. Clinically, most imaging modalities are based on anatomy and provide limited information about the on-going molecular activities affecting the vulnerability of atherosclerotic lesion for risk stratification of patients. Thus, the ability to differentiate stable plaques from those that are vulnerable is an unmet clinical need. Of various imaging techniques, the radionuclide-based molecular imaging modalities including positron emission tomography and single-photon emission computerized tomography provide superior ability to noninvasively visualize molecular activities in vivo and may serve as a useful tool in tackling this challenge. Moreover, the well-established translational pathway of radiopharmaceuticals may also facilitate the translation of discoveries from benchtop to clinical investigation in contrast to other imaging modalities to fulfill the goal of precision medicine. The relationship between inflammation occurring within the plaque and its proneness to rupture has been well documented. Therefore, an active effort has been significantly devoted to develop radiopharmaceuticals specifically to measure CVD inflammatory status, and potentially elucidate those plaques which are prone to rupture. In the following review, molecular imaging of inflammatory biomarkers will be briefly discussed.

Ketosis prevents abdominal aortic aneurysm rupture through C-C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance.

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase and received daily ß-aminopropionitrile to promote AAA rupture. Rats with AAAs received either a standard diet, ketogenic diet (KD), or exogenous KBs (EKB). Rats receiving KD and EKB reached a state of ketosis and had significant reduction in AAA expansion and incidence of rupture. Ketosis also led to significantly reduced aortic CCR2 content, improved MMP balance, and reduced ECM degradation. Consistent with these findings, we also observed that Ccr2-/- mice have significantly reduced AAA expansion and rupture. In summary, this study demonstrates that CCR2 is essential for AAA expansion, and that its modulation with ketosis can reduce AAA pathology. This provides an impetus for future clinical studies that will evaluate the impact of ketosis on human AAA disease.