Yagna PR Jarajapu

North Dakota State University | NDSU · Department of Pharmaceutical Science

Background The APP/PS1 mouse model recapitulates pathology of human Alzheimer’s disease (AD). While amyloid-β peptide deposition and neurodegeneration are features of AD, the pathology may involve inflammation and impaired vascular regeneration. Objective This study evaluated inflammatory environments in the brain and bone marrow (BM), and the imp...

Tumor-derived extracellular vesicles (EVs) show great potential as biomarkers for several diseases, including pancreatic cancer, due to their roles in cancer development and progression. However, the challenge of utilizing EVs as biomarkers lies in their inherent heterogeneity in terms of size and concentration, making accurate quantification diffi...

Background: Diet-induced obesity (DIO) increases risk for cardiovascular disease largely due to compromised gut barrier integrity and systemic inflammation. Animal models for understanding the pathophysiology of complications associated with DIO do not take address the genetic factors, which determine the individual variation in the susceptibility...

Angiotensin (Ang)-(1–7) stimulates vasoprotective functions of diabetic (DB) CD34⁺ hematopoietic stem/progenitor cells partly by decreasing reactive oxygen species (ROS), increasing nitric oxide (NO) levels and decreasing TGFβ1 secretion. Telomerase reverse transcriptase (TERT) translocates to mitochondria and regulates ROS generation. Alternative...

Compromised barrier function of colon epithelium with aging is largely due to gut microbial dysbiosis. Recent studies implicate an important role for angiotensin converting enzymes, ACE and ACE2, angiotensins, and the receptors, AT1 receptor (AT1R) and Mas receptor (MasR), in the regulation of colon functions. This study tested the hypothesis that...

Lillquist, T, Mahoney, SJ, Kotarsky, C, McGrath, R, Jarajapu, Y, Scholten, SD, and Hackney, KJ. The effect of direct and remote postexercise ischemic conditioning on muscle soreness and strength 24 hours after eccentric drop jumps. J Strength Cond Res XX(X): 000-000, 2022-Strategic limb occlusion applied after exercise may facilitate recovery, not...

The expression of the angiotensin-converting enzyme 2 (ACE2) is altered in multiple chronic kidney diseases like hypertension and renal fibrosis, where the signaling from the basal membrane proteins is critical for the development and progression of the various pathologies. Integrins are heterodimeric cell surface receptors that have important role...

Aging is associated with chronic systemic inflammation largely due to increased myelopoiesis, which in turn increases risk for vascular disease. We have previously shown evidence for the therapeutic potential of Angiotensin-(1–7) (Ang-(1–7)) in reversing vasoreparative dysfunction in aging. This study tested the hypothesis that ischemic vascular re...

Cardiovascular protective axis of Renin Angiotensin System is relatively newer concept and largely originated from the discoveries of an alternative angiotensin-converting enzyme (ACE), ACE2 and a heptapeptide metabolite of RAS angiotensin-(1–7) (Ang-(1–7)). The property of ACE2 to cleave angiotensin II (Ang II), which produces pathological effects...

Cardiovascular protective axis of Renin Angiotensin System is relatively newer concept and largely originated from the discoveries of an alternative angiotensin-converting enzyme (ACE), ACE2 and a heptapeptide metabolite of RAS angiotensin-(1–7) (Ang-(1–7)). The property of ACE2 to cleave angiotensin II (Ang II), which produces pathological effects...

Background: Advancing of age decreases the barrier properties of intestinal epithelium which leads to sterile systemic inflammation. Chronic low-grade chronic inflammation is an underlying cause for the age-related comorbidities such as cardiovascular disorders. Renin Angiotensin System (RAS) plays an important role in the homeostasis of cardiovas...

Aging is associated with impaired vascular repair following ischemic insult, largely due to reparative dysfunctions of progenitor cells. Activation of Mas receptor (MasR) was shown to reverse aging-associated vasoreparative dysfunction. This study tested the impact of MasR-deficiency on mobilization and vasoreparative functions with aging. Wild typ...

Diabetes increases risk for ischemic vascular diseases, which is further elevated in older adults. Bone marrow-derived hematopoietic CD34+ stem/progenitor cells have the potential of re- revascularization however diabetes attenuates vasoreparative functions. ACE2 is the vasoprotective enzyme of renin angiotensin system in contrast to the canonical...

Aging increases risk for ischemic vascular diseases. Bone marrow–derived hematopoietic stem/progenitor cells (HSPCs) are known to stimulate vascular regeneration. Activation of either the Mas receptor (MasR) by angiotensin-(1-7) (Ang-(1-7)) or angiotensin-converting enzyme-2 (ACE2) stimulates vasoreparative functions in HSPCs. This study tested if...

Adult CD34 ⁺ hematopoietic stem/progenitor cells (HSPC) in the systemic circulation are bone marrow-derived and have the propensity of maintaining cardiovascular health. Activation of Angiotensin Converting enzyme-2 (ACE2)/Angiotensin-(1-7)/Mas receptor pathway, the vascular protective axis of renin angiotensin system (RAS), stimulates vasculogenic...

Bone marrow-derived hematopoietic stem/progenitor cells are vasculogenic, and play an important role in endothelial health and vascular homeostasis by participating in post-natal vasculogenesis. Progenitor cells are mobilized from bone marrow niches in response to remote ischemic injury and migrate to the areas of damage and stimulate revasculariza...

Bone marrow derived monocyte-macrophages promote healing of injured tissue cooperatively with vasculogenic hematopoietic stem/progenitor cells. However, diabetes dysregulates hematopoiesis and attenuates bone marrow-derived tissue-reparative responses. In a recent issue of The Journal of Pathology, Barman et al. extensively characterized myelopoiet...

Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) are mobilized into the circulation in response to ischemic injury and stimulate vascular regeneration. Angiotensin-(1-7) (Ang-(1-7)) activates vasoprotective functions in progenitor cells by activating Mas receptor (MasR). We have shown that mobilization of progenitor cells in response...

CD34⁺ hematopoietic stem/progenitor cells (HSPCs) are vasculogenic and hypoxia is a strong stimulus for the vasoreparative functions of these cells. Angiotensin‐converting enzyme 2 (ACE2)/angiotensin‐(1–7)/Mas receptor (MasR) pathway stimulates vasoprotective functions of CD34⁺ cells. This study tested if ACE2 and MasR are involved in the hypoxic s...

Adult CD34 ⁺ hematopoietic stem/progenitor cells in the systemic circulation are bone marrow‐derived and have the propensity of maintaining cardiovascular health. We have previously shown that activation of the vascular protective axis of renin angiotensin system (RAS), Angiotensin Converting enzyme‐2 (ACE2)/Angiotensin‐(1–7)/Mas receptor axis stim...

Bone marrow‐derived hematopoietic stem progenitor cells (HSPCs) have vasoreparative functions and are physiologically mobilized into circulation. Aging or diabetes increases risk for cardiovascular diseases and are known to be associated with impaired HSPC functions. Angiotensin converting enzyme (ACE) and ACE2 are primary enzymes of cardiovascular...

Background and purpose: The opioid crisis in the United States is widespread and requires large scale efforts to reduce the problem. A recent call by the American Association of Colleges of Pharmacy requested commitments by member schools to enact curricular changes in order to prepare pharmacy graduates to be impactful in addressing the opioid cr...

Background and Purpose CD34⁺ haematopoietic stem/progenitor cells have revascularization potential and are now being tested for the treatment of ischaemic vascular diseases in clinical trials. We tested the hypothesis that mitochondrial depolarization stimulates the reparative functions of CD34⁺ cells. Experimental Approach Peripheral blood was ob...

Adult bone marrow‐derived CD34 ⁺ cells have the propensity of re‐endothelialization and vascular generation, and are currently being investigated for the potential benefit in the treatment of ischemic vascular diseases. Activation of the cardiovascular‐protective axis of renin angiotensin system, Angiotensin Converting Enzyme‐2 (ACE2)/Angiotensin‐(...

Bone marrow progenitor cells (BMPCs) are mobilized into the systemic circulation and maintain cardiovascular health. We have recently showed that Mas receptor (MasR) is a promising approach for reversing the impaired mobilization of BMPCs, in conditions such as diabetes. This study investigated the role of endogenous MasR expression in BMPC mobiliz...

Diazoxide is a selective activator of mitochondrial ATP‐sensitive potassium channel (mitoK ATP ), which causes mitochondrial depolarization, and is known to be protective in ischemic conditions. Bone marrow derived CD34 ⁺ hematopoietic stem/progenitor cells have vascular‐reparative functions and are now being tested for their potential benefit for...

Abstract P247: ACE2/ACE Imbalance in the Placental Circulation in an Ovine Model of Intrauterine Growth Restriction Shrinidh Joshi, Caleb O Lemley, Kimberly A Vonnahme, and Yagna P Jarajapu Originally published 6 Dec 2018. https://doi.org/10.1161/hyp.72.suppl_1.P247 Hypertension. 2018;72:AP247 Abstract Intrauterine growth restriction (IUGR) has bee...

Telomerase reverse transcriptase (TERT) has been shown to translocate to mitochondria (mtTERT), and decrease the generation of mitochondrial reactive oxygen species (mtROS). Angiotensin (Ang)-(1-7) stimulates vasoreparative functions in diabetic CD34 ⁺ stem/progenitor cells in part by decreasing ROS levels and increasing nitric oxide (NO) bioavaila...

CD34 ⁺ stem/progenitor cells have the propensity of re-endothelialization and vascular regeneration. Angiotensin Converting Enzyme-2 (ACE2) generates Angiotensin (Ang)-(1-7), which produces vasoprotection by acting on Mas receptor (MasR). Hypoxic preconditioning has been shown to stimulate vascular repair-relevant functions of CD34 ⁺ cells, which w...

Adult bone marrow‐derived hematopoietic stem/progenitor cells (HSPCs) have the propensity of re‐endothelialization and revascularization following ischemic vascular damage. Diabetes is associated with severe impairment in pharmacological mobilization of HSPCs by granulocyte‐colony stimulating factor (G‐CSF) or plerixafor. Leptin, an adipocyte‐deriv...

CD34 ⁺ hematopoietic stem/progenitor cells (HSPCs) have the propensity of re‐endothelialization and vascular regeneration. Angiotensin Converting Enzyme‐2 (ACE2) generates the heptapeptide, Angiotensin (Ang)‐(1‐7), which produces vasoprotective effects by acting on Mas receptor (MasR). We have previously reported that hypoxic preconditioning robust...

Hematopoietic stem/progenitor cells (HS/PCs) have the propensity of ischemic vascular repair, and this innate vasoprotective function is impaired in diabetes. Angiotensin-converting enzyme (ACE) and ACE-2 are primary enzymes of the cardiovascular-detrimental and protective axes of the renin-angiotensin system, respectively. In this study, we tested...

In recent years, previously unknown functions have been conferred to the RAAS and have been explored in mechanistic studies and disease models. Implication of bone marrow stem/progenitor cells in the cardiovascular protective or detrimental effects of RAAS is a prominent advancement because of the translational significance. Selected members of RAA...

Ang-(1-7)/MasR pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of Ang-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. Study was carried out in streptozotocin-induced diabetic or db/db mice. Diabetes resulted in decreased number of Linea...

Angiotensin (Ang)-(1-7)/Mas receptor (MasR) pathway accelerates vascular repair in ischemic conditions partly by stimulating the mobilization of vascular reparative bone marrow progenitor cells (BMPCs) into blood circulation. This study tested if the endogenous MasR expression is required for the mobilization of BMPCs in response to ischemic injury...

Diabetes is associated with impaired mobilization of bone marrow stem/progenitor cells that accelerate vascularization of ischemic areas. This study characterized mobilization of vascular reparative bone marrow progenitor cells in mouse models of diabetes. Age-matched control or streptozotocin (STZ)-induced diabetic, and db/db mice with lean-contro...

Bone marrow stem/progenitor cells (BMSPCs) are mobilized in response to ischemic injury. BMSPCs accelerate vascular repair by re‐endothelialization and revascularization of ischemic areas. Long‐term diabetes causes impairment of mobilization, a.k.a. stem cell mobilopathy, which has now been considered as a major contributing factor for the developm...

CD34 ⁺ hematopoietic stem cells are now known for their cardiovascular regenerative functions, and provide a breakthrough approach for the treatment of ischemic cardiovascular diseases. Vasorepairative functions of these cells are known to be potentiated by exposure to hypoxia. Previous studies have demonstrated that nitric oxide (NO) derived from...

Angiotensin-converting enzymes, ACE and ACE2, are key members of renin angiotensin system. Activation of ACE2/Ang-(1-7) pathway enhances cardiovascular protective functions of bone marrow-derived stem/progenitor cells. The current study evaluated the selectivity of ACE2 inhibitors, MLN-4760 and DX-600, and ACE and ACE2 activities in human (hu) and...

CD34(+) stem/progenitor cells have been identified as a promising cell population for the autologous cell-based therapies in patients with cardiovascular disease. The two axes of renin angiotensin system, ACE/Ang II/AT1 receptor and ACE2/Ang-(1-7)/Mas receptor, play an important role in the cardiovascular repair. This study evaluated the vascular r...

Background: Leptin, an adipocyte-derived hormone, elicits a variety of physiological functions by acting on leptin receptor (LepR). LepR is expressed in bone marrow hematopoietic stem/progenitor cells (BMSPCs) as well as in mesenchymal stromal cells, which play an important role in the maintenance and retention of BMSPCs. Cytokines such as G-CSF in...

We hypothesized that endothelial progenitor cells derived from individuals with diabetes would exhibit functional defects including inability to respond to hypoxia and altered paracrine/autocrine function that would impair the angiogenic potential of these cells. Circulating mononuclear cells isolated from diabetic (n = 69) and nondiabetic (n = 46)...

Introduction Angiotensin (Ang)-(1-7) is a recently identified vasoprotective heptapeptide, and it appears to activate the reparative functions of bone marrow–derived stem/progenitor cells (BMPCs). Aim This study evaluated the effect of Ang-(1-7) in the angiogenic function of cavernosum in type 1 diabetes (T1D) and delineated the role of BMPCs in t...

Angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang)-(1-7), key members of the vasoprotective axis of the renin-angiotensin system (RAS), have been shown to modulate hematopoietic functions of bone marrow-derived cells. This coupled with recent studies implicating the involvement of bone marrow stem/progenitor cells in the cardiovascular fu...

We hypothesized that endothelial progenitor cells derived from individuals with diabetes would exhibit functional defects including inability to respond to hypoxia and altered paracrine/autocrine function that would impair the angiogenic potential of these cells. Circulating mononuclear cells isolated from diabetic (n = 69) and nondiabetic (n = 46)...

The success of autologous cell therapies for the treatment of cardiovascular disease in patients with diabetes is dependent on mobilization of bone marrow derived stem/progenitor cells (BMSPCs). We tested the efficacy of bone marrow (BM) mobilizing agents in experimental diabetes. Mice with Streptozotocin‐induced type 1 diabetes were used either at...

Mobilization of bone marrow stem/progenitor cells (BMSPCs) that maintain cardiovascular health is impaired in diabetes. We have previously shown that Angiotensin (Ang)‐(1‐7) increases the vasoreparative potential of dysfunctional BMSPCs from individuals with diabetes. In this study we tested the effect of Ang‐(1‐7) on the impaired mobilization of B...

Angiotensin (Ang)‐(1–7), a metabolite of Angiotensin‐converting enzyme‐2 (ACE2), is cardiovascular protective. Recent studies have implicated an important role of angiogenic progenitor cells (APCs) in the functions of Ang‐(1–7). This study evaluated the effect of Ang‐(1–7) in the tissue angiogenesis independent of APCs. Strips of corpus cavernosum...

Diabetes increases the risk for cardiovascular disease due to impaired function and regeneration of endothelium. Mobilization of bone marrow stem/progenitor cells (BMPCs) that regenerate vascular endothelium, is impaired in diabetes. Angiotensin (Ang)‐(1–7) was shown to increase the vasoreparative potential of diabetic BMPCs. This study evaluates t...

The use of opioids, which achieve therapeutic analgesia through activation of μ-opioid receptors, are limited in the management of chronic pain by adverse effects including tolerance and addiction. Optogenetics is an emerging approach of designing molecular targets that can produce cell-specific receptor-mediated analgesia with minimal side effects...

Rationale: Studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays a protective role against lung diseases, including pulmonary hypertension (PH). Recently, an antitrypanosomal drug, diminazene aceturate (DIZE), was shown to exert an "off-target" effect of enhancing the enzymatic activity of ACE2 in vitro. Objectives: To eval...

We tested the hypothesis that activation of the protective arm of the renin angiotensin system (RAS), the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD34(+) cells from patients...

Aims/hypothesis: We sought to determine the impact of long-standing type 1 diabetes on haematopoietic stem/progenitor cell (HSC) number and function and to examine the impact of modulating glycoprotein (GP)130 receptor in these cells. Methods: Wild-type, gp130(-/-) and GFP chimeric mice were treated with streptozotocin to induce type 1 diabetes....

Previously, we showed that insulin growth factor (IGF)-1 binding protein-3 (IGFBP-3), independent of IGF-1, reduces pathological angiogenesis in a mouse model of the oxygen-induced retinopathy (OIR). The current study evaluates novel endothelium-dependent functions of IGFBP-3 including blood retinal barrier (BRB) integrity and vasorelaxation. To ev...

Discovery of angiotensin converting enzyme (ACE)-2 provided a strong impetus for the development of novel therapeutic tools for the treatment of cardiovascular diseases (CVDs). Angiotensin (Ang)-(1-7), the product of ACE2, via activation of Mas receptor elicits cardiovascular protective effects to a large extent by counter-regulating ACE/Ang-II/AT1...

The peptide hormone relaxin is a potent vasodilator with therapeutic potential in diseases complicated by vasoconstriction, including heart failure. However, the molecular mediators and magnitude of vasodilation may vary according to duration of exposure and artery type. The objective of these studies was to determine mechanisms of rapid (within mi...

The vasodegenerative phase of diabetic retinopathy is likely caused by endothelial dysfunction and reduced endothelial repair. Migration of endothelial progenitor cells (EPCs) into areas of vascular injury is critical to vascular repair. This key function, often defective in diabetes, is largely mediated by nitric oxide (NO), which is known to be i...

Angiotensin II (Ang II) type AT(1) receptors expressed on vascular smooth muscle cells (VSMCs) couple to the Jak2 signalling pathway. However, the importance of this tissue-specific coupling is poorly understood. The purpose of this investigation was to determine the importance of VSMC-derived Jak2 in angiotensin II-mediated hypertension. The Cre-l...

1601 Objective The dysfunction of human diabetic CD34+ endothelial progenitor cells limits their utility in autologous cell therapy for vascular complications. Previously, we showed that transient inhibition of transforming growth factor-beta 1 (TGF-β1) enhances vascular reparative function of human CD34+ cells isolated from diabetics (Bhatwadekar...

2637 Purpose RAS plays a vital role in regulating many physiological processes of the vascular system. Angiotensin II (Ang II), a product of angiotensin converting enzyme (ACE), mediates its effects through activation of either the AT1 receptor – to induce vasoconstriction, proliferation, fibrosis, and inflammation – or the AT2 receptor to promote...

Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabe...

We have previously showed that inhibition of NADPH oxidase corrected diabetic migratory defect in circulating putative endothelial progenitor cells (CD34+) by decreasing the production of reactive oxygen species (ROS) thereby increasing intracellular nitric oxide (NO). In this study, we evaluated the effect of NADPH oxidase blockade on the vascular...

We have previously reported that myogenic tone in ophthalmic artery is impaired in obese type‐2 diabetic BBZDR/Wor rat. In this study, we delineated the role of endothelium‐derived reactive oxygen species (ROS) in the attenuated myogenic response. Ophthalmic arteries were isolated from BBZDR/Wor rats (T2D) with 4–5 months duration of diabetes and t...

Dysfunction of endothelial nitric oxide synthase (eNOS) has been implicated in the pathogenesis of diabetic vascular complications. This study was undertaken to determine the role of eNOS in the development of diabetic retinopathy (DR), by investigating the functional consequences of its deficiency in the diabetic state. Diabetes was induced in eNO...

The discovery of endothelial progenitor cells (EPCs) in human peripheral blood advanced the field of cell-based therapeutics for many pathological conditions. Despite the lack of agreement about the existence and characteristics of EPCs, autologous EPC populations represent a novel treatment option for complications requiring therapeutic revascular...

Purpose: To test the hypothesis that BMDC of diabetic (D) origin have impaired responsiveness to the hypoxic microenvironment and ineffective paracrine signaling. Methods: FACS sorted CD34+ and CD14+ cells from D and non diabetic (n=10) (ND) individuals (n=10) were exposed to normoxia (pO2=40 mmHg) or hypoxia (pO2=5 mmHg). Levels of HIF1- α and sur...

Purpose: We recently reported the vascular protective effect of IGFBP3 in experimental models of ischemic vascular injury involving increased homing of circulating endothelial progenitor cells and activation of nitric oxide synthase (eNOS). The vascular protective potential of a molecule is determined in part by its ability to facilitate perfusion...