Abstract Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial ‘Ischemia No Obstructive Coronary Artery disease’ (INOCA). In the present study, we tested hypothesis results in perturbations perfusion oxygen delivery using a novel swine model multiple comorbidities. DM (streptozotocin),...

Heart failure with a preserved ejection fraction (HFpEF) is associated multiple comorbidities, such as old age, hypertension, type 2 diabetes and obesity more prevalent in females. Although the male obese ZSF1 rat has been proposed suitable model to study development of diastolic dysfunction early HFpEF, studies female animals have not performed yet. Therefore, we aimed characterize cardiac phenotype rats their lean counterparts. Additionally, investigate whether differences exist disease...

Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress produced endothelial dysfunction, altering control tone via loss NO bioavailability, which was associated with an increase circulating endothelin (ET). In the present study, we tested hypotheses (1) ROS scavenging (2) ET

Abstract In the present study, we tested hypothesis that multiple risk factors, including diabetes mellitus (DM), dyslipidaemia and chronic kidney disease (CKD) result in a loss of nitric oxide (NO) signalling, thereby contributing to coronary microvascular dysfunction. Risk factors were induced 12 female swine by intravenous streptozotocin injections high fat diet (HFD) renal artery embolization (CKD). Female healthy ( n = 13) on normal served as controls (Normal). After 5 months,...

Abstract Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control a DM + HC CKD swine model. 6 months after induction of CKD, arterial pressure was similar chronically instrumented female ( n = 19) Healthy 18). However,...

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main source(s): Dutch CardioVascular Alliance (an initiative with support the Heart Foundation) Grant 2020B008 RECONNEXT, and German Center for Cardiovascular Research (DZHK; 81Z0600207) Background failure preserved ejection fraction lacks targeted therapies, due to insufficient understanding pathogenesis. A multiple comorbidity swine model (MCS) was developed by exposure three risk factors six...

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main source(s): Dutch Cardiovascular Alliance Background/Objectives We have previously shown, in female swine that the combination three cardiovascular risk factors (diabetes mellitus (DM), hypercholestolemia (HC) and chronic kidney disease (CKD)) induces systemic inflammation, oxidative stress, coronary endothelial dysfunction impaired myocardial perfusion due to nitric oxide (NO)...

Abstract Background Coronary microvascular angina occurs in both men and women, however, the majority of patients are postmenopausal women with multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) dyslipidemia. No treatment is available for coronary dysfunction, requiring more depth knowledge on mechanisms underlying this syndrome expanding group patients. Purpose Here we studied function vivo vitro isolated small arteries, post-menopausal...

Abstract Introduction Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD) may contribute to myocardial “Ischemia No Obstructive Coronary Artery disease” (INOCA). Purpose We studied perfusion oxygen delivery using a novel swine model multiple comorbidities. Methods DM (streptozotocin), HFD (high fat diet) CKD (renal embolization), were induced in 12 female...

Multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia are known to induce inflammation microvascular dysfunction contributing impaired myocardial perfusion. We previously observed that a combination of DM, high fat diet (HFD) CKD produced an increase in coronary tone awake swine, resulting perturbations O 2 balance. The increased was mediated by NO bioavailability accompanied levels reactive oxygen species (ROS) circulating...

Abstract Background Diabetes mellitus (DM), chronic kidney disease (CKD) and consumption of a high-fat diet (HFD), are well known risk factors for diastolic heart failure. We recently developed multiple comorbidity swine model (MCS), with DM (streptozotocin), HFD CKD (kidney embolization), showed that 6 months sustained hyperglycemia, hypercholesterolemia dysfunction resulted in inflammation oxidative stress associated coronary microvascular left ventricular dysfunction. Additionally, MCS...

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired left ventricular (LV) relaxation and filling due to increased myocardial stiffness hypertrophy. The development of HFpEF associated multiple, interrelated risk factors including obesity, chronic kidney disease (CKD), diabetes mellitus (DM), hypertension. Mechanistic studies have implied that comorbidity-driven inflammation, oxidative stress, endothelial dysfunction act as contributors the...

Abstract Background Multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia are known to induce inflammation microvascular dysfunction contributing impaired myocardial perfusion. We previously observed that a combination of DM, high fat diet (HFD) CKD produced an increase in coronary tone awake swine, resulting perturbations O2 balance. The increased was mediated by NO bioavailability accompanied levels reactive oxygen species (ROS)...

CAD and comorbidities 1405CKD patients compared to matched controls, the effect of apabetalone treatment on those pathways.Results: Apabetalone PK parameters were similar in controls CKD patients.At baseline, plasma proteomics showed enrichment markers that correlate with progression CKD, as including cystatin C b2 microglobulin (3-fold 5-fold enrichment, respectively, p<0.001).Accordingly, pathway analysis proteome at baseline an upregulation pathways underlie CVD such inflammatory...

Background Multiple comorbidities, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD) are thought to cause coronary microvascular dysfunction through a reduction in NO signaling, leading impaired myocardial perfusion. Here we investigated whether NO‐cGMP‐PDE5 signaling is modified swine with DM+HC+CKD, by studying the vasodilator responses PDE5 inhibition exogenous chronically instrumented swine. Methods results Five female (DM+HC+CKD) Diabetes...

Comorbidities such as diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are often associated with diastolic dysfunction. We tested the hypothesis that co‐morbidities produce systemic inflammation microvascular dysfunction resulting in impaired myocardial perfusion, structural changes myocardium well cardiac swine. Methods Results DM (streptozotocin, 150mg/kg i.v.), HC (high fat diet) CKD (renal artery embolization), (DM+HC+CKD) were induced 16 female swine,...

Introduction Multiple comorbidities, including diabetes mellitus (DM), hypercholesterolemia, hypertension (HT) and chronic kidney disease (CKD) are thought to cause coronary microvascular dysfunction reduce NO‐production, leading impaired myocardial perfusion contributing the development of left ventricular diastolic dysfunction. In present study, we aimed investigate detrimental effects DM, CKD high fat diet (HFD) on function blood flow regulation role NO bioavailability herein in swine....

Introduction Multiple comorbidities, including diabetes mellitus (DM), hypercholesterolemia and chronic kidney disease (CKD) are associated with diastolic dysfunction. These risk factors also cause coronary microvascular dysfunction leading to impaired myocardial perfusion ischemia non‐obstructive artery (INOCA). Recently a link has been proposed between INOCA HFpEF. We investigated the detrimental effects of DM, CKD high fat diet (HFD) on function perfusion. Hypothesis Prolonged exposure...

Introduction Diabetes mellitus (DM), chronic kidney disease (CKD) and hypercholesterolemia are common co‐morbidities associated with low‐grade inflammation endothelial dysfunction leading to increased systemic vascular resistance, diastolic exercise intolerance. Diastolic is a risk factor for development of post‐capillary pulmonary hypertension (PH), which, in subgroup patients, deteriorates into combined pre‐and PH. This process characterized by an increase resistance (PVR) due remodeling....