Minocycline, an anti-inflammatory antibiotic drug, rebalances impaired gut microbiota, attenuates neuroinflammation and lowers high blood pressure in animal models of hypertension and in hypertensive patients. Our objective in this study was to investigate if antihypertensive effects of minocycline involve the expression of gut epithelial genes relevant to blood pressure homeostasis using human colonic 3-dimensional organoid culture and high-throughput RNA sequencing. The data demonstrates that minocycline could restore impaired expression of functional genes linked to viral and bacterial immunity, inflammation, protein trafficking and autophagy in human hypertensive organoids.
View Article and Find Full Text PDFBackground: Pulmonary hypertension (PH), characterized by elevated pulmonary pressure and right heart failure, is a systemic disease involving inappropriate sympathetic activation and an impaired gut-brain-lung axis. Global overexpression of angiotensin converting enzyme 2 (ACE2), a cardiopulmonary protective enzyme of the renin-angiotensin system, attenuates PH induced by chronic hypoxia. Neurons within the paraventricular nucleus of the hypothalamus (PVN) that synthesize corticotropin-releasing hormone (CRH) are activated by stressors, like hypoxia, and this activation augments sympathetic outflow to cardiovascular tissues.
View Article and Find Full Text PDFHypertension (HTN) is associated with gut dysbiosis and the depletion of butyrate-producing bacteria in animal models and people. Furthermore, fecal material transfer from donor hypertensive patients increases blood pressure in normotensive recipient animals and ameliorates HTN-associated pathophysiology. These observations have implications in the impaired interactions between the gut and gut microbiota in HTN.
View Article and Find Full Text PDFBackground Hypertension is associated with gut dysbiosis, altered intestinal immunity, and gut pathology in animal models and humans. Although these findings have implicated impaired interactions between gut and gut microbiota in hypertension, little is known about the specific functional gut microbes that interact with intestinal mucosa. Methods and Results To identify these microbes, we sorted Immunoglobin A (IgA)-coated (IgA) and IgA-noncoated (IgA) bacteria using a combination of magnetic-activated cell sorting and fluorescence-activated cell sorting, and subsequently performed 16 S rRNA gene sequencing (IgA-SEQ) to determine the microbial composition of IgA and IgA fractions in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats.
View Article and Find Full Text PDFBackground: Despite the availability of various classes of antihypertensive medications, a large proportion of hypertensive individuals remain resistant to treatments. The reason for what contributes to low efficacy of antihypertensive medications in these individuals is elusive. The knowledge that gut microbiota is involved in pathophysiology of hypertension and drug metabolism led us to hypothesize that gut microbiota catabolize antihypertensive medications and compromised their blood pressure (BP)-lowering effects.
View Article and Find Full Text PDFRecent evidence suggests pulmonary hypertension (PH), a disease of the pulmonary vasculature actually has multiorgan pathophysiology and perhaps etiology. Herein, we demonstrated that fecal matter transplantation from angiotensin-converting enzyme 2 overexpressing mice counteracted the effects of chronic hypoxia to prevent pulmonary hypertension, neuroinflammation, and gut dysbiosis in wild type recipients.
View Article and Find Full Text PDFHypertension is a worldwide problem with major impacts on health including morbidity and mortality, as well as consumption of health care resources. Nearly 50% of American adults have high blood pressure, and this rate is rising. Even with multiple antihypertensive drugs and aggressive lifestyle modifications, blood pressure is inadequately controlled in about 1 of 5 hypertensive individuals.
View Article and Find Full Text PDFHypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation.
View Article and Find Full Text PDFIntroduction: Antihypertensive medication nonadherence is a prevalent issue but is very difficult to accurately assess. To clarify this problem among hypertensive patients attending a cardiovascular disease outpatient clinic, we utilized high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) to assess antihypertensive medication adherence and identify trends by sex and drug class.
Methods: Serum was extracted from blood samples obtained from patients with either drug-controlled or drug resistant hypertension (RHTN) and analyzed via HPLC-MS for antihypertensive drugs which were categorized by drug class as beta blockers, aldosterone antagonists, diuretics, ACE inhibitor/ARBs, or calcium channel blockers.
Background: Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote "meta-organisms," such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts' gut/brain axis physiology.
View Article and Find Full Text PDFThe rapid spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought into focus the key role of angiotensin-converting enzyme 2 (ACE2), which serves as a cell surface receptor required for the virus to enter cells. SARS-CoV-2 can decrease cell surface ACE2 directly by internalization of ACE2 bound to the virus and indirectly by increased ADAM17 (a disintegrin and metalloproteinase 17)-mediated shedding of ACE2. ACE2 is widely expressed in the heart, lungs, vasculature, kidney and the gastrointestinal (GI) tract, where it counteracts the deleterious effects of angiotensin II (AngII) by catalyzing the conversion of AngII into the vasodilator peptide angiotensin-(1-7) (Ang-(1-7)).
View Article and Find Full Text PDFPurpose Of Review: Rapidly emerging evidence implicates an important role of gut-brain-bone marrow (BM) axis involving gut microbiota (GM), gut epithelial wall permeability, increased production of pro-inflammatory BM cells and neuroinflammation in hypertension (HTN). However, the precise sequence of events involving these organs remains to be established. Furthermore, whether an impaired gut-brain-BM axis is a cause or consequence of HTN is actively under investigation.
View Article and Find Full Text PDFThe angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin-angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein-coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models.
View Article and Find Full Text PDFDiscovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, BAT1, in gut.
View Article and Find Full Text PDFEmerging evidence implicates an interplay among multiple organs such as brain, vasculature, gut and lung in the development of established pulmonary arterial hypertension (PAH). This has led us to propose that activated microglia mediated-enhanced sympathetic activation contributes to PAH pathophysiology. Since enhanced sympathetic activity is observed in human PAH and the gut is highly innervated by sympathetic nerves that regulate its physiological functions, we hypothesized that PAH would be associated with gut pathophysiology.
View Article and Find Full Text PDFTherapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH.
View Article and Find Full Text PDFWe have previously found that in utero exposure to excess maternal cortisol (1 mg/kg/day) in late gestation increases the incidence of stillbirth during labor and produces fetal bradycardia at birth. In the interventricular septum, mitochondrial DNA (mt-DNA) was decreased, and transcriptomics and metabolomics were consistent with altered mitochondrial metabolism. The present study uses transcriptomics to model effects of increased maternal cortisol on fetal biceps femoris.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is considered a disease of the pulmonary vasculature. Limited progress has been made in preventing or arresting progression of PAH despite extensive efforts. Our previous studies indicated that PAH could be considered a systemic disease since its pathology involves interplay of multiple organs.
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