Adding the value of the Charlson Comorbidity Index to the GRACE score for mortality prediction in acute coronary syndromes.

BACKGROUND: Scarce and conflicting data still exist about the role of the Charlson Comorbidity Index (CCI) when added to the traditional Global Registry of Acute Coronary Events (GRACE) risk score for outcome prediction in patients with acute coronary syndrome (ACS). METHODS: All consecutive admissions due to ACS, from 1 January 2018 to 31 December 2020 were retrospectively reviewed from an internal database of a tertiary cardiac center in Salerno (Italy). Logistic and Cox proportional regression analyses were performed in order to assess the contribution of the CCI on 30-day and long-term mortality. The CCI adding value to the GRACE score was analyzed with several measures of improvement in discrimination: increase in the area under the receiver-operating characteristic curve (AUC), the integrated discrimination improvement (IDI), and the categorical and continuous net reclassification improvement (cNRI) more than 0. Robustness of the results was assessed through an internal validation procedure with bootstrapping. RESULTS: One thousand three hundred and ten patients were identified. The median age was 68 (58-78) years. One hundred and twenty (9.2%) and 113 (9.5%) deaths occurred, respectively, during the first 30 days from admission and during long-term follow-up (median follow-up time: 13 months; interquartile range: 9-24). After multivariate regression analysis, the CCI was not associated with short-term mortality, while it was significantly and independently associated with long-term mortality along with the GRACE score (hazard ratio: 1.34, 95% confidence interval: 1.22-1.47; P  < 0.001). An additive effect of CCI with the GRACE risk score was observed in predicting long-term mortality: AUC from 0.768 to 0.819 ( P  = 0.003), category-based NRI: 0.215, cNRI>0: 0.669 ( P  < 0.001), IDI: 0.066 ( P  < 0.001). CONCLUSION: The CCI is a predictor of long-term mortality and improves risk stratification of patients with ACS over the GRACE risk score.

Sacubitril/Valsartan vs. Standard Medical Therapy on Exercise Capacity in HFrEF Patients.

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5-22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study's primary end-point was the change from baseline in peak VO2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.

Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF.

AIMS: The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success. METHODS AND RESULTS: From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability. CONCLUSIONS: Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses.

Predictors of complications in initially haemodynamically stable patients admitted in a modern coronary care unit.

AIMS: Resource optimization in the intensive cardiac care unit (ICCU) is, nowadays, of great importance because of the increasing number of acute cardiovascular patients requiring high-intensity level-of-care. Because of natural limits in ICCU bed availability, understanding, which patients will really benefit from in a such a critical care setting, is of paramount importance. In our study, we analysed a heterogeneous ICCU population with initially stable haemodynamic conditions, in order to find potential predictors of severe complications. METHODS: Nine hundred and fifty patients admitted to our ICCU during the year 2019 were screened in order to detect those with a stable haemodynamic condition at admission. Data were extrapolated from an internal database. Comorbidity burden was expressed by the Charlson Comorbidity Index (CCI). Our primary end point was defined by a combination of severe complications requiring critical care, and in-hospital death. RESULTS: Ninety-eight patients (14.1% of 695 stable patients identified) developed severe complications. After a multivariable logistic regression analysis, four predictors were identified: signs of congestive heart failure [OR: 9.25, 95% confidence interval (CI): 5.61-15.25; P < 0.001], SBP 120 mmHg or less (OR: 2.10, 95% CI: 1.27-3.47; P = 0.004), haemoglobin level 13 g/dl or less (OR: 1.75, 95% CI: 1.03-2.95; P = 0.037), and the CCI above 3 (OR: 2.27, 95% CI: 1.13-4.56; P = 0.022). CONCLUSION: In our study, 73% of patients showed a stable haemodynamic condition on admission. Severe complications occurred in 14.1% of these patients, and signs of heart failure were the main determinants of the outcome. SBP, haemoglobin level, and the CCI concurred in the prediction of severe complications during the hospital stay.

Intensive cardiac care unit admission trends during the COVID-19 outbreak in Italy: a multi-center study.

A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (- 35%) and acute coronary syndrome (ACS; - 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (- 49%) and NSTEMI (- 61%) compared to men (- 28%) and STEMI (- 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization.

Predictors of in-hospital and long-term mortality in unselected patients admitted to a modern coronary care unit.

AIMS: Objective data on epidemiology, management and outcome of patients with acute cardiac illness are still scarce, and producing evidence-based guidelines remains an issue. In order to define the clinical characteristics and the potential predictors of in-hospital and long-term mortality, we performed a retrospective, observational study, in a tertiary cardiac centre in Italy. METHODS: One thousand one hundred and sixty-five consecutive patients, admitted to our intensive cardiac care unit (ICCU) during the year 2016, were included in the study. The data were collected from the hospital discharge summary and the electronic chart records. RESULTS: Global in-hospital mortality was 7.2%. Predictors of in-hospital mortality were age [odds ratio (OR): 2.0; P = 0.011], female sex (OR: 2.18; P = 0.003), cardiac arrest (OR: 12.21; P = 0.000), heart failure/cardiogenic shock (OR: 9.99; P = 0.000), sepsis/septic shock (OR: 5.54; P = 0.000), acute kidney injury (OR: 3.25; P = 0.021) and a primary diagnosis of acute heart failure or a condition other than acute heart failure and acute coronary syndrome. During a mean follow-up period of 17.4 ± 4.8 months, 96 all-cause deaths occurred in patients who were still alive at discharge. One-year mortality rate was 8.2%. Predictors of long-term mortality were age (hazard ratio: 1.08; P = 0.000), female sex (hazard ratio: 0.59; P = 0.022), comorbidity at least 3 (hazard ratio: 1,60; P = 0.047), acute kidney injury (hazard ratio: 3.15; P = 0.001), inotropic treatment (hazard ratio: 2.54; P = 0.002) and a primary diagnosis of acute heart failure. CONCLUSION: In our Level-2 ICCU, predictors of in-hospital and long-term mortality are similar to those commonly found in a Level-3 ICU. These data strongly suggest that ICUs dealing with acute cardiovascular patients should be reorganized with a necessary upgrading of competences and resources for medical and nursing staff.

Surgical management of a free-floating thrombus in the ascending aorta.

The ascending aorta is an uncommon site of noninfective thrombus. We describe the case of a 63-year-old woman who was admitted to our department with acute myocardial infarction. Coronary angiography showed occlusion of a small diagonal vessel, likely related to a distal embolization event. A transthoracic echocardiogram revealed a free-floating mass in the proximal ascending aorta. Two-and 3-dimensional transesophageal echocardiography studies were performed, and after a multidisciplinary heart team discussion, surgical removal of the mass was planned and successfully performed through a median sternotomy on cardiopulmonary bypass.

Primary percutaneous coronary intervention during ST elevation myocardial infarction in prosthetic valve endocarditis: a case report.

BACKGROUND: Infective endocarditis (IE) is still a condition with high mortality and morbidity, especially in the elderly, and in patients with prosthetic valves. The concept of "time-to-therapy" plays a key role for the prompt management of IE and related complications, and the currently available multimodality imaging may play a key role in this setting. Myocardial ischemia due to extrinsic coronary compression from an aortic abscess is an extremely rare condition where the optimal therapeutic strategy has not been defined yet. We present herein the first case of a patient with ST elevation myocardial infarction caused by an aortic root abscess treated with percutaneous stent implantation. CASE PRESENTATION: An 82-year-old woman with a history of atrial fibrillation, chronic renal failure, anemia and a bioprosthetic aortic valve replacement performed in 2014, was admitted to hospital with profound asthenia and a pyrexia of unknown origin. Because of high clinical suspicion of endocarditis, a trans-esophageal echocardiogram was performed. Empirical broad-spectrum antimicrobial therapy was initiated, followed by targeted treatment based on the results of blood cultures (Staphylococcus aureus). The echocardiogram did not show vegetations and the patient was managed conservatively. She suddenly deteriorated, due to an acute coronary syndrome (ACS) with anterior ST segment elevation. An urgent angiogram was performed, and extrinsic compression of the left coronary system, due to an aortic root abscess, was suspected. After discussion with the surgical team, percutaneous revascularization was attempted, aiming to restore satisfactory hemodynamics, in order to plan surgery. Unfortunately, the patient rapidly developed cardiogenic shock, with multi organ failure, and died in less than 24 h. CONCLUSIONS: Patients with fever, and significant risk factors for endocarditis, who develop ACS, need a prompt diagnostic work up, including trans-esophageal echocardiography. At present, the specific timing of echocardiographic follow-up and surgical intervention is still a matter of debate, and our case aims to highlight the importance of this aspect in the management of endocarditis, in order to avoid severe complications that adversely affect patient prognosis.

Persistent Unexplained Dyspnea: A Case of Hepatopulmonary Syndrome.

Regarding a patient with dyspnea, the history and physical examination often lead to the correct diagnosis. In some circumstances, when more than one underlying disease is present, the diagnostic process can be more challenging. We describe an unusual case of dyspnea and persistent hypoxemia related to a hepatopulmonary syndrome in a 53-year-old patient with known heart failure and chronic liver disease. Initially managed with intravenous diuretic therapy, due to signs of lung and peripheral congestion, our patient did not improve as expected; therefore we performed more advanced studies with a chest-abdomen CT scan and a right heart catheterization. They showed, respectively, no signs of parenchymal and vasculature lung disease, a cirrhotic liver disease, splenomegaly, signs of portal hypertension, and high cardiac output with normal pulmonary vascular resistance. These results, along with the association of hypoxemia and chronic liver disease, suggested a hepatopulmonary syndrome. The diagnosis was confirmed by the demonstration of an intrapulmonary vascular dilatation with right to left shunt during a microbubble transthoracic echocardiography and a lung perfusion scan. Liver transplantation is the only successful treatment for this syndrome; however, the patient became soon unsuitable for this strategy, due to a rapid clinical deterioration.

Cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

A 62-year-old woman with multiple myeloma and light-chain amyloidosis with significant heart involvement developed an in-hospital cardiac arrest. After cardiopulmonary resuscitation, a stable sinus rhythm without any cerebral damage was restored, and the patient was admitted to the coronary care unit. A cardioverter-defibrillator was implanted, and it successfully intervened in two sustained ventricular tachycardia episodes and one ventricular fibrillation episode, which were recorded during hospitalization. After achieving discrete cardiac compensation, the patient was transferred to the emergency medicine department where she underwent chemotherapy for multiple myeloma. The patient died 40 days after admission from refractory heart failure. In the literature, there are studies that describe the use of cardioverter-defibrillator implantation in cardiac amyloidosis; however, at present, there is no evidence of a beneficial effect on survival with the use of this intervention. A high index of suspicion for amyloid heart disease and early diagnosis are critical to improving outcomes.

Retrograde dissection during percutaneous coronary intervention: sealing of the entry site by covered stent implantation.

We present a case of iatrogenic aortic haematoma, developed during percutaneous coronary intervention, treated with covered stent implantation followed by a conservative approach characterised by the integration of both clinical and multimodal imaging information. This complication can lead to overt aortic dissection (28-47%), rupture (20-45%) or death (21%). In 10% of the cases it can completely regress. Guidelines for its treatment are debated because of the unpredictable natural history of intramural haematoma. Nowadays, a close follow-up with multimodal imaging is considered a valid strategy for the appropriate management of this severe condition. On the basis of the patient's clinical condition and the information obtained by multiple imaging tests (angiography, transthoracic and transesophageal echocardiography and multidetector CT scan) we decided to treat our patient with medical therapy. To date, a 1-year follow-up negative for cardiac events is recorded.

GRK2 levels in umbilical arteries of pregnancies complicated by gestational hypertension and preeclampsia.

BACKGROUND: G-Protein coupled receptor kinase 2 (GRK2) represents a regulator of cell function in different cardiovascular conditions, including high blood pressure. The relationship between elevated GRK2 levels and impaired vasorelaxant responses is causative of hypertension through the increase in vascular resistances. The aim of this study is to ascertain if this feature is present in the fetal placental vasculature of pregnancies complicated by hypertensive disorders. METHODS: We have assessed GRK2 levels in the umbilical arteries (UA) of 21 preeclamptic or gestational hypertensive and 23 normotensive women at time of delivery. RESULTS: GRK2 levels were increased in the hypertensive group (0.83 ± 0.14 vs. 0.48 ± 0.06 densitometry units; P < 0.05). GRK2 levels were in correlation and in linear regression with systolic, diastolic, and mean arterial pressure (P < 0.05, r(2) = 0.12, r(2) = 0.11, r(2) = 0.12). Correlations did not reach a significant value for other clinical parameters such as gestational age at birth, umbilical artery pulsatility index, maternal proteinuria, and neonatal birth weight. Out of the 21 hypertensive women, 7 who developed a preeclampsia associated with early preterm delivery (before 34 weeks) had a significantly lower GRK2 levels compared to the remaining 14 (0.51 ± 0.12 vs. 1.08 ± 0.20 densitometry units, P < 0.05). CONCLUSIONS: We conclude that elevated GRK2 levels in the umbilical vasculature is correlated to elevated blood pressure levels, with a likely compensatory rather than causative role since the lack of protective effect of elevated GRK2 levels may negatively affect the outcome of the hypertensive state.

Multiple coronary artery thrombosis in 5,10-methylenetetrahydrofolate reductase gene mutation.

A 42-year-old man presented at our attention with chest pain. His cardiac risk factors were smoking habit and family history of coronary artery disease. At the ECG, a mild ST-segment elevation in the inferior leads was shown. A normal left ventricular function was demonstrated at the echocardiography. An emergency coronary angiography was performed, and an extensive thrombosis of the right coronary artery and midleft anterior descending coronary artery was visualized. A primary angioplasty with thrombus aspiration and direct stenting of both sites followed. Biochemical analysis revealed a high plasma homocysteine level with a homozygotic anomaly of the 5,10-methylenetetrahydrofolate reductase. Currently, a nine-month followup negative for cardiac events is recorded.

G protein-coupled receptor kinase 2 in patients with acute myocardial infarction.

Lymphocyte G protein-coupled receptor kinase 2 (GRK2) levels are increased in patients with chronic heart failure, and in this condition, they correlate with cardiac function. The aim of this study was to assess the prognostic role of GRK2 during acute cardiac dysfunction in humans. A study was designed to investigate the role of GRK2 levels in patients with acute coronary syndromes. Lymphocyte GRK2 levels were examined at admission and after 24 and 48 hours in 42 patients with acute coronary syndromes, 32 with ST-segment elevation myocardial infarction and 10 with unstable angina as a control group. Echocardiographic parameters of systolic and diastolic function and left ventricular remodeling were evaluated at admission and after 2 years. GRK2 levels increased during ST-segment elevation myocardial infarction and were associated with worse systolic and diastolic function. This association held at 2-year follow-up, when GRK2 was correlated with the ejection fraction and end-systolic volume, indicating a prognostic value for GRK2 levels during acute ST-segment elevation myocardial infarction. In conclusion, lymphocyte GRK2 levels increase during acute myocardial infarction and are associated with worse cardiac function. Taken together, these data indicate that GRK2 could be predictive of ventricular remodeling after myocardial infarction and could facilitate the tailoring of appropriate therapy for high-risk patients.

A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFkappaB activity.

BACKGROUND: Based on its role in angiogenesis and apoptosis, the inhibition of NFkappaB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFkappaB, thus we evaluated its effects on cancer growth. METHODS: The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. RESULTS: In vitro, adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IkappaB accumulation and inhibits NFkappaB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFkappaB activity, an increase of IkappaB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. CONCLUSION: Our data suggest that GRK5-RH inhibition of NFkappaB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer.

The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance.

AIMS: Insulin (Ins) resistance (IRES) associates to increased cardiovascular risk as observed in metabolic syndrome. Chronic stimulation of beta-adrenergic receptors (betaAR) due to exaggerated sympathetic nervous system activity is involved in the pathogenesis of IRES. The cellular levels of G protein coupled receptor kinase 2 (GRK2) increase during chronic betaAR stimulation, leading to betaAR desensitization. We tested the hypothesis that GRK2 plays a role in betaAR-induced IRES. METHODS AND RESULTS: We evaluated Ins-induced glucose uptake and signalling responses in vitro in cell overexpressing the beta(2)AR, the GRK2, or the catalytically dead mutant GRK2-DN. In a model of increased adrenergic activity, IRES and elevated cellular GRK2 levels, the spontaneously hypertensive rats (SHR) we performed the intravenous glucose tolerance test load. To inhibit GRK2, we synthesized a peptide based on the catalytical sequence of GRK2 conjugated with the antennapedia internalization sequence (Ant-124). Ins in human kidney embryonic (HEK-293) cells causes rapid accumulation of GRK2, tyrosine phosphorylation of Ins receptor substrate 1 (IRS1) and induces glucose uptake. In the same cell type, transgenic beta(2)AR overexpression causes GRK2 accumulation associated with significant deficit of IRS1 activation and glucose uptake by Ins. Similarly, transgenic GRK2 overexpression prevents Ins-induced tyrosine phosphorylation of IRS1 and glucose uptake, whereas GRK2-DN ameliorates glucose extraction. By immunoprecipitation, GRK2 binds IRS1 but not the Ins receptor in an Ins-dependent fashion, which is lost in HEK-GRK2 cells. Ant-124 improves Ins-induced glucose uptake in HEK-293 and HEK-GRK2 cells, but does not prevent GRK2/IRS1 interaction. In SHR, Ant-124 infusion for 30 days ameliorates IRES and IRS1 tyrosine phosphorylation. CONCLUSION: Our results suggest that GRK2 mediates adrenergic IRES and that inhibition of GRK2 activity leads to increased Ins sensitivity both in cells and in animal model of IRES.

In vivo properties of the proangiogenic peptide QK.

The main regulator of neovascularization is Vascular Endothelial Growth Factor (VEGF). We recently demonstrated that QK, a de novo engineered VEGF mimicking peptide, shares in vitro the same biological properties of VEGF, inducing capillary formation and organization. On these grounds, the aim of this study is to evaluate in vivo the effects of this small peptide. Therefore, on Wistar Kyoto rats, we evaluated vasomotor responses to VEGF and QK in common carotid rings. Also, we assessed the effects of QK in three different models of angiogenesis: ischemic hindlimb, wound healing and Matrigel plugs. QK and VEGF present similar endothelium-dependent vasodilatation. Moreover, the ability of QK to induce neovascularization was confirmed us by digital angiographies, dyed beads dilution and histological analysis in the ischemic hindlimb as well as by histology in wounds and Matrigel plugs. Our findings show the proangiogenic properties of QK, suggesting that also in vivo this peptide resembles the full VEGF protein. These data open to new fields of investigation on the mechanisms of activation of VEGF receptors, offering clinical implications for treatment of pathophysiological conditions such as chronic ischemia.

G-protein-coupled receptor kinases in cardiovascular conditions: focus on G-protein-coupled receptor kinase 2, a gain in translational medicine.

With increasing knowledge of the regulatory mechanisms of G-protein-coupled receptor signaling in heart physiology, many studies have focused on the role of this system in cardiovascular disease. In recent years, scientists have moved their attention from the receptors to their regulatory proteins: the G-protein-coupled receptor kinases. This class of protein is indispensable for terminating signaling of G-protein-coupled receptors through receptor desensitization and downregulation. This article attempts to assemble the currently available information regarding G-protein-coupled receptor kinases and their role in cardiovascular disease and, in particular, the potential employment of G-protein-coupled receptor kinase 2 as biomarker of cardiac dysfunction.