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Background and Aims: Atherosclerosis is a degenerative process of the arterial wall implicating activation of macrophages and proliferation of vascular smooth muscle cells. Calcium-calmodulin dependent kinase type II (CaMKII) in vascular smooth muscle cells (VSMCs) regulates proliferation, while in macrophages, this kinase governs diapedesis, infiltration and release of extracellular matrix enzymes. We aimed at understanding the possible role of CaMKII in atherosclerosis plaques to regulate plaque evolution towards stability or instability., Methods: Clinically defined stable and unstable plaques obtained from patients undergoing carotid end arteriectomy were processed for evaluation of CaMKs protein expression, activity and localization., Results: The larger content of CaMKII was found in CD14 + myeloid cells that were more abundant in unstable rather than stable plaques. To test the biological effect of activated CD14 + myeloid cells, VSMCs were exposed to the conditioned medium (CM) of macrophages extracted from carotid plaques. CM induced attenuation of CaMKs expression and activity in VSMCs, leading to the reduction of VSMCs proliferation. This appears to be due to the CaMKII dependent release of cytokines., Conclusions: These results indicate a pivotal role of CaMKs in atherosclerosis by regulating activated myeloid cells on VSMCs activity. CaMKII could represent a possible target for therapeutic strategies based on macrophages specific inhibition for the stabilization of arteriosclerotic lesions., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

Large numbers of patients with severe peripheral arteriopathic disorders (Stage IV) present a characteristic clinical history of pain and ulcerative trophic lesions requiring either major or minor amputation. Recent studies have shown that L-propionyl-carnitine (LPC) can possibly moderate the tissue damage induced by ischaemia in peripheral arteriopathic disorders. In the present study 12 patients with severe obstructive chronic arteriopathy were treated either with 2 g of LPC (plus heparin and buflomedil) by slow infusion b.i.d, or by placebo plus heparin and buflomedil. In the LPC-treated patients, one lesion was completely healed (17%); two showed a > 50% decrease in the surface of the ulcerative lesion (34%) and three a reduction in such surface < 50% (50%). Control patients showed a reduction < 50% of the ulcerative lesions in two cases (34%), unaltered limits of the ulcer margin in three cases (50%) and worsening of such a lesion in one case. In addition, the LPC-treated patients showed a progressive reduction in the evening pain symptom as monitored by the fewer requested doses of the analgesic compound ketoprofen (77 vs 125 requests for administration in treated and control patients, respectively). The long-term effect of LPC treatment evaluated after three months showed that in treated patients only one minor (digital) amputation was performed, whereas in the control group two patients underwent minor (digital and foot) and one major (above knee) amputations. In conclusion, the results of the present preliminary study suggest that LPC administration can improve the healing of ulcerative lesions, can reduce the need for analgesic medication and can lessen the incidence of amputation.