Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.

Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

Carotid Pseudoaneurysm After Eversion Endarterectomy: A Case Report and Review of the Literature.

BACKGROUND: Pseudoaneurysm (PA) after carotid endarterectomy (CEA) is a rare and potentially life-threatening complication, with an incidence lower than 1%. Most of the cases described report PAs after carotid patch angioplasty and are associated with infection, often caused by Staphylococci. The management of PAs can be surgical, endovascular, or hybrid. METHODS: We herein present the case of an infected carotid PA 27 days after an eversion CEA. We performed a common to internal carotid bypass with the interposition of great saphenous vein (GSV) associated with specific polyantibiotic therapy for 4 weeks. We searched the PubMed database for reviews and cases reports for patients who developed carotid PA after primary repair CEA in the period between 1969 and 2017. RESULTS: We identified 21 cases of primary closure post-CEA PAs in the literature. In almost 60% of patients, infection was detected. Open surgery was performed in all the cases; in 1 case, an hybrid approach was preferred. In 52% of cases, a vein graft/patch or primary closure was chosen; in 3 cases, ligation was preferred, and in 1 case, a polyester graft was used. CONCLUSION: In our experience and with the evidence observed in the literature, open surgery with GSV interposition is the safest treatment in infected carotid PAs. The endovascular approach must be performed only in proven noninfectious cases. A bridge technique with the insertion of a stent followed by open surgery repair can be an option in emergency cases.

Delivery of Chlamydia pneumoniae to the vessel wall aggravates atherosclerosis in LDLr-/- mice.

OBJECTIVE: The role of Chlamydia pneumoniae in atherosclerosis is still debated. In this study a novel mouse model was applied to determine the direct impact of C. pneumoniae on the arterial wall and the development of atherosclerosis. METHODS: Direct effects of C. pneumoniae on collar-induced atherosclerosis were studied after local delivery of C. pneumoniae to carotid arteries of LDL receptor-deficient (LDLr-/-) mice. RESULTS: The presence of C. pneumoniae in the vessel wall was quantified by RT-PCR (6.2 x 10(4) copies/artery) and resulted in a 2.0-fold increase in intima/media ratios (p<0.05) and a 1.7-fold increase in stenosis (p<0.05). Immunostaining revealed a 2.98-fold (p<0.01) increased macrophage content and a tendency towards lower numbers of smooth muscle cells and collagen in lesions of infected carotid arteries. Direct delivery of another respiratory pathogen, Mycoplasma pneumoniae, to the carotids did not affect size or composition of the atherosclerotic lesions. Presence of C. pneumoniae in the carotid arteries resulted within 7 days in a marked upregulation of the expression of MCP-1 (p<0.01) and ICAM-1 as determined on mRNA and protein levels. These in vivo data were in line with data obtained with in vitro infections of macrophages and endothelial cells with C. pneumoniae. CONCLUSIONS: We conclude that C. pneumoniae in carotid arteries leads to more pronounced atherosclerotic lesions with a more vulnerable morphology and that this model is suitable to monitor direct effects of C. pneumoniae on atherogenesis.

Selection of cell specific peptides in a rat carotid injury model using a random peptide-presenting bacterial library.

Cell specific peptides are possible candidates to enable targeted delivery of drugs and therapeutic genes in vivo. This study explores the utility of using a peptide-presenting bacterial library (pFliTrx) for the selection of new cell specific peptides, which bind to vascular cells of perfused tissues or organs. The balloon-injured rat carotid artery served as a model. Following perfusion of injured vascular segments with pFliTrx, 36 single clones could be identified. In radioligand binding studies, one of them, peptide P36, binds predominantly to perfused injured versus control vessel segments. It was additionally found that P36 binds with a 700-fold higher affinity in vitro to endothelial cells stimulated by treatment with LPS and TNF-alpha compared with unstimulated endothelial cells. The amino acid sequence of P36 reveals high homology to alpha(4)beta(1)-integrin, which mediates leukocyte migration from the vasculature at sites of inflammation via binding to cellular adhesion molecules, such as VCAM. In summary, this study demonstrates, that high specific peptides directed against injured vascular cells can be selected using a random peptide-presenting bacterial library.

Immunity to heat shock protein 65--an additional determinant in intimal thickening.

Inflammation occurring consequent to vessel injury is thought to play an important role in atherosclerosis and restenosis. Autoimmunity to HSP65 has been shown to accelerate early atherogenesis in rabbits and mice, whereas in humans epidemiological data support this contention. In the current study, we explored the possibility of HSP65 influencing the extent of neointimal growth in the rat carotid injury model. Rats were either immunized with recombinant mycobacterial HSP65, heat killed preparation of Mycobacterium tuberculosis (MT), or with PBS, all emulsified in incomplete Freund's adjuvant. Animals were boosted with a similar protocol 3 weeks following the primary immunization and 2 weeks later carotid injury was applied in all animals by balloon inflation. Upon sacrifice 2 weeks later, sera were obtained for measurement of anti-HSP65 antibodies by ELISA, splenocytes were assessed for proliferative response to in vitro priming with HSP65, and carotid arteries were removed for evaluation of neointimal growth. Rats immunized with HSP65 exhibited a brisk and sustained humoral immune response to HSP65, and cellular immunity was also evident by thymidine uptake to splenocytes primed with the respective protein. Neointimal/medial ratio was significantly increased in HSP65 immunized rats, in comparison with MT injected and control animals. In conclusion, immunity to HSP65 can play a role in accelerating restenosis following arterial injury. These results should be further investigated in humans as they may provide a possible link between infections and restenosis/accelerated arteriosclerosis.

Endovascular coiling of a mycotic external carotid artery pseudoaneurysm following pharyngolaryngectomy with a free jejunal graft.

OBJECTIVES: (1) To highlight the significance of carotid artery pseudoaneurysm as a rare complication following neck dissection, and (2) to suggest endovascular coiling as management, in the presence of infection, previous radiotherapy and a grafted blood supply. CASE REPORT: A 66-year-old man diagnosed with squamous cell carcinoma of the hypopharynx and upper oesophagus underwent pharyngolaryngectomy with reconstruction of a neo-pharynx using a free jejunal graft. The patient had previously received radiotherapy for a soft palate squamous cell carcinoma. Two months after surgery, computed tomography demonstrated a bilobed pseudoaneurysm of the left external carotid artery just distal to the arterial branch supplying the jejunal graft. This mycotic pseudoaneurysm was successfully treated with endovascular coiling, while maintaining the patency of the superior thyroid artery supplying the jejunal graft anastomosis. CONCLUSION: In this patient, endovascular coiling of the external carotid artery was considered to be the only definitive treatment for a life-threatening mycotic pseudoaneurysm.

Carotid artery rupture and cervicofacial actinomycosis.

Cervicofacial actinomycosis is an uncommon, progressive infection caused by bacilli of the Actinomyces genus. Actinomyces are common commensal saprophytes in the oral cavity which may have medical importance as facultative pathogens. Subsequent to local injuries to the oral mucosa, they may penetrate the deep tissues and be responsible for suppurative or granulomatous infections. We herein report a case of a 65-year-old man who underwent surgery followed by chemotherapy and radiotherapy for a tonsillar carcinoma. An ulcerous lesion in the base of the tongue developed and spread to the carotid artery wall. The man died of a massive hemorrhage due to left carotid artery rupture. Postmortem computed tomography angiography performed prior to autopsy allowed the precise localization of the source of bleeding to be detected. Postmortem biochemical investigations confirmed the presence of inflammation associated with local bacterial infection. Histological investigations revealed the rupture of the left carotid artery surrounded by numerous colonies of Actinomyces. Acute and chronic inflammation with tissue necrosis as well as post-actinic, fibrotic changes were also found in the tissues surrounding the ruptured artery wall.

Infectious pseudoaneurysm of the internal carotid artery treated with a covered stent.

Rapidly expanding infectious pseudoaneurysms of the internal carotid artery can have deleterious consequences. A patient is reported who presented with such an aneurysm. The morphology of the aneurysm was not amenable to microsurgical treatment. The aneurysm was successfully treated with covered stents. This is only the third report of a patient with an infectious pseudoaneurysm in the internal carotid artery treated with a covered stent. At the 1 year follow-up visit, the patient continues to do well.

A successful combined endovascular and surgical treatment of a cranial base mucormycosis with an associated internal carotid artery pseudoaneurysm.

OBJECTIVE: We report a rare case of internal carotid artery pseudoaneurysm owing to rhinocerebral mucormycosis and review 40 reported cases from 1980 to present. CLINICAL PRESENTATION: A 38-year-old Caucasian man presented with a 3-day history of headache, diplopia, and numbness in the distribution of the left ophthalmic and maxillary branches of the trigeminal nerve. A complete left cavernous syndrome was discovered upon neurological examination. Magnetic resonance imaging scans revealed an inflammatory process involving the paranasal sinuses with extension into the left cavernous sinus, temporal fossa, and petrous bone. INTERVENTION: The patient was immediately treated with amphotericin B, atorvastatin, and daily hyperbaric oxygen sessions before surgical intervention. The patient underwent endovascular treatment of the associated mycotic pseudoaneurysm after carotid test occlusion in addition to a radical bilateral debridement of the paranasal sinuses and infratemporal and temporal fossa. CONCLUSION: Aggressive multimodal therapy is imperative for late-stage rhinocerebral mucormycosis. Extensive resection of infected tissue combined with amphotericin B, atorvastatin, and hyperbaric oxygen seems to be the best course of management. If the internal carotid artery is involved, endovascular intervention is clearly an option to attain this goal. Further research and longer follow-up periods are required to better understand the long-term implications of endovascular coiling and hyperbaric oxygen therapy for rhinocerebral mucormycosis.