Our data suggest that adaptive optics has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, as WLR measured with adaptive optics is more closely correlated with the M/L of subcutaneous small arteries (r = 0.84, P < 0.001 vs. r = 0.52, P < 0.05, slopes of the relations: P < 0.01 adaptive optics vs. SLDF). In addition, the reproducibility of the evaluation of the WLR with adaptive optics is far better, as compared with SLDF, as intraobserver and interobserver variation coefficients are clearly smaller. This may be important in terms of clinical evaluation of microvascular morphology in a clinical setting, as micromyography has substantial limitations in its clinical application due to the local invasiveness of the procedure.

Pharmacological inhibition of VEGF-VEGFR is now a cornerstone in the treatment of many malignancies; however, treatment with VEGF inhibitors is commonly associated with an increase in blood pressure values. This side effect is strictly connected with the mechanism of action of these medications and might represent an index of therapy efficacy. The optimal management of this form of hypertension is, at present, not clear. Calcium channel blockers and renin-angiotensin system inhibitors probably represent the most appropriate classes of hypertensive dugs for the treatment of this condition; however, no conclusive data are presently available.

ObjectiveIt has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in hypertension. In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while T-regulatory (Treg) lymphocytes seem to be protective in this regard. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed.Design and methodsWe have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 12 hypertensive lean subjects undergoing an elective surgical intervention. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and Treg lymphocytes.ResultsA marked reduction of several Treg subpopulations was observed in obese patients compared with controls, together with an increased in CD4+ effector memory T-effector cells.ConclusionIn severely obese patients, Treg lymphocytes are clearly reduced and CD4+ effector memory cells are increased. It may be hypothesized that they might contribute to the development of marked microvascular alterations previously observed in these patients.

Treatment with exenatide, but not with liraglutide, was able to increase the number of circulating EPCs, possibly through an antioxidative/antiinflammatory effect.

Objective: Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density.Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study.Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months.Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.

Our results indicate that, in small resistance arteries of patients with essential hypertension, a relevant fibrosis may be detected; fibronectin and TGF-β1 tunica media content is increased, while laminin and emilin-1 content is decreased; these changes might be involved in the development of small resistance artery remodeling in humans.

Cardiovascular diseases represent the leading cause of death in Western Countries. Among them, a key role is played by arterial hypertension, which causes macro-and microvascular alterations. Specifically, hypertension is associated with structural alterations in the microvessels, such as an increased ratio of the tunica media thickness to internal lumen (M/L ratio) in small resistance arteries and a reduction of capillary density. In order to evaluate the small resistance artery structure, the direct measurements of M/L ratio through wire or pressure micromyography has been considered the gold-standard method. Despite the availability of convincing evidence about the prognostic relevance of the M/L ratio, the invasiveness of these methods has limited its implementation in the daily clinical practice. Therefore, non-invasive techniques have been developed to evaluate microvascular morphology, particularly in the retina, since it is perhaps the most accessible microvasculature. Scanner laser Doppler flowmetry (SLDF) and adaptive optics (AO) represent the most promising approaches for the evaluation of morphological characteristics of retinal arterioles, in particular for the measurement of their wall-to-lumen ratio (W/L ratio). The possibility to evaluate microvascular morphology by non-invasive techniques represents a major clinical advancement, with possibly favorable implications in research and in stratification of cardiovascular risk. In this review we will address the different methods to investigate the microcirculation as well as their clinical usefulness.

Dihydropyridine calcium channel blockers may possess antioxidant properties, and might improve micro and macrovascular structure and function. Combination treatment with an ACE inhibitor may have additional advantages, compared with a thiazide diuretic. The aim of the present study is to investigate the effects of a short-term treatment with lercanidipine, and to compare two combination treatments: lercanidipine + enalapril vs. lercanidipine + hydrochlorothiazide on structural alterations in retinal arterioles, on skin capillary density and on large artery distensibility. Thirty essential hypertension patients are included in the study, and treated for 4 weeks with lercanidipine 20 mg per day orally. Then, they were treated for 6 months with lercanidipine + enalapril (n = 15) or lercanidipine + hydrochlorothiazide (n = 15) combinations. Investigations were performed on basal condition, after appropriate wash out of previous treatments, after 4 weeks of lercanidipine monotherapy treatment, and at the end of the combination treatment. Non-invasive measurements of wall-to-lumen ratio (WLR) and other morphological parameters of retinal arterioles were performed using either scanning laser Doppler flowmetry or adaptive optics. Capillary density was evaluated by capillaroscopy, while pulse wave velocity was measured, and central blood pressures were assessed by pressure waveform analysis. A significant improvement of WLR and other indices of retinal artery structure is observed with both technical approaches after treatment with lercanidipine alone, with a further improvement after treatment with lercanidipine + enalapril, while after treatment with lercanidipine + hydrochlorothiazide, the improvement is partially blunted. Central systolic and diastolic blood pressures are similarly reduced by both therapeutic strategies. Capillary density is increased only after treatment with lercanidipine + enalapril. In conclusion, lercanidipine both in monotherapy and in combination with enalapril but not with hydrochlorothiazide is able to improve microvascular structure; on the other hand, a decrease in central blood pressure is observed with both therapeutic combinations