Biomimetic MRI contrast agent for imaging of inflammation in atherosclerotic plaque of ApoE-/- mice: a pilot study.

Objective: Atherosclerosis involves an inflammatory process characterized by cellular and molecular responses. A slow-clearance blood-pool paramagnetic agent (CMD-A2-Gd-DOTA: P717) chemically modified to create a functionalized product (F-P717) for targeting inflammation in vessel walls was evaluated in vivo in mice.

Methods And Results: Carboxylate and sulfate groups were grafted onto the macromolecular paramagnetic Gd-DOTA-dextran backbone.

Increased insulin-stimulated expression of arterial angiotensinogen and angiotensin type 1 receptor in patients with type 2 diabetes mellitus and atheroma.

Objective: Because inhibition of the renin-angiotensin system (RAS) reduces the onset of type 2 diabetes (T2D) and prevents atherosclerosis, we investigated the expression of RAS in the arterial wall of T2D and nondiabetic (CTR) patients.

Methods And Results: mRNA and protein levels of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AT1 receptor (AT1R) were determined in carotid atheroma plaque, nearby macroscopically intact tissue (MIT), and in vascular smooth muscle cells (VSMCs) before and after insulin stimulation from 21 T2D and 22 CTR patients. AGT and ACE mRNA and their protein levels were 2- to 3-fold higher in atheroma and in MIT of T2D patients.

Reduced atherosclerotic lesion size in P-selectin deficient apolipoprotein E-knockout mice fed a chow but not a fat diet.

P-selectin. We investigated the role of P-selectin on the development of vascular lesions in an ApoE(-/-) male mice. Double-knockout (ApoE(-/-), P-selectin(-/-); DKO) were compared to single-knockout (ApoE(-/-); SKO) mice.

Induction of tissue kallikrein in human carotid atheroma does not lead to kallikrein-kinins pathway activation.

Objective: The impairment of the tissue kallikrein-kinin system (KKS) may result in atheroma development. To determine the involvement of KKS in pathophysiology of human atherosclerosis, we examined the expression of all components of this system as well as angiotensinogen (another tissue kallikrein (TK) substrate), at messenger ribonucleic acid (mRNA) and protein levels in the human carotid artery with and without atheroma.

Methods: mRNA levels were compared with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) between atheroma plaque and intact tissue obtained during carotid endarterectomy in 15 patients.