-
Journal of the American Heart... Jun 2024The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We...
BACKGROUND
The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration.
METHODS AND RESULTS
C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca activated K BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes.
CONCLUSIONS
Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.
PubMed: 38904226
DOI: 10.1161/JAHA.123.033558 -
Microvascular Research Jun 2024Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular...
Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I. HO enhanced I and ET-1 production. Enhancing I caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.
PubMed: 38901735
DOI: 10.1016/j.mvr.2024.104699 -
Biology of Sex Differences Jun 2024Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and...
BACKGROUND
Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A (TxA) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment.
METHODS
Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O) or hypoxia (11% O) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence.
RESULTS
Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels.
CONCLUSIONS
Prenatal hypoxia increased TxA vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring.
Topics: Animals; Female; Rats, Sprague-Dawley; Pregnancy; Vasoconstriction; Male; Prenatal Exposure Delayed Effects; Thromboxane A2; Sex Characteristics; Antioxidants; Nitric Oxide; Mesenteric Arteries; Rats; Hypoxia; Fetal Hypoxia; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
PubMed: 38898532
DOI: 10.1186/s13293-024-00627-x -
Animal Models and Experimental Medicine Jun 2024Under hypoxia, exaggerated compensatory responses may lead to acute mountain sickness. The excessive vasodilatory effect of nitric oxide (NO) can lower the hypoxic...
BACKGROUND
Under hypoxia, exaggerated compensatory responses may lead to acute mountain sickness. The excessive vasodilatory effect of nitric oxide (NO) can lower the hypoxic pulmonary vasoconstriction (HPV) and peripheral blood pressure. While NO is catalyzed by various nitric oxide synthase (NOS) isoforms, the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear. Therefore, this study aims to investigate the regulatory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.
METHODS
Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (N-nitro-D-arginine methyl ester, D-NAME), L-NAME group (non-selective NOS inhibitor, N-nitro-L-arginine methyl ester), AG group (inducible NOS inhibitor group, aminoguanidine), and 7-NI group (neurological NOS inhibitor, 7-nitroindazole). Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia [15% O, 2200 m a. sl., 582 mmHg (76.5 kPa), Xining, China] using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo. Serum NO concentrations and blood gas analysis were measured.
RESULTS
Under normoxia, mean arterial pressure and total peripheral vascular resistance were increased, and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups. During hypoxia, pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.
CONCLUSIONS
This compensatory mechanism activated by inducible NOS and endothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress. It plays a crucial role in alleviating hypoxia-induced pulmonary arterial hypertension.
PubMed: 38888011
DOI: 10.1002/ame2.12453 -
Journal of Pain Research 2024We aimed to assess uterine and arcuate artery Doppler indices in patients with mild primary dysmenorrhea.
PURPOSE
We aimed to assess uterine and arcuate artery Doppler indices in patients with mild primary dysmenorrhea.
PATIENTS AND METHODS
A total of 55 patients were included, consisting of women without dysmenorrhea (n=26, group A) and women with mild primary dysmenorrhea (n=29, group B). Doppler measurements of the uterine and arcuate arteries were performed in both groups on the 1st-2nd days and 21st-24th days (midluteal phase) of the menstrual cycle using transvaginal ultrasound and compared between the groups. The severity of dysmenorrhea was assessed using visual analog scale scores.
RESULTS
Doppler measurements of the uterine and arcuate arteries performed on the 1st-2nd days of the menstrual cycle and the midluteal phase were similar between the groups (p>0.05). There was a significant decrease in the intragroup measurements of uterine and arcuate arteries performed on the first day of menstruation and the luteal phase in both groups (p<0.01).
CONCLUSION
Doppler findings of the uterine and arcuate arteries did not differ between patients with and without mild primary dysmenorrhea. The etiology of primary dysmenorrhea mainly involves ischemia and vasoconstriction, but mild primary dysmenorrhea appears to be associated with a different etiology other than decreased tissue perfusion.
PubMed: 38887385
DOI: 10.2147/JPR.S456239 -
Thyroid Research Jun 2024Primary hypothyroidism (PHT) is associated with an increased risk for the development of atherosclerosis (AS) and other cardiovascular disorders. PHT induces... (Review)
Review
Primary hypothyroidism (PHT) is associated with an increased risk for the development of atherosclerosis (AS) and other cardiovascular disorders. PHT induces atherosclerosis (AS) through the induction of endothelial dysfunction, and insulin resistance (IR). PHT promotes vasoconstriction and the development of hypertension. However, patients with subclinical PHT with normal thyroid hormones (THs) are also at risk for cardiovascular complications. In subclinical PHT, increasing thyroid stimulating hormone (TSH) levels could be one of the causative factors intricate in the progression of cardiovascular complications including AS. Nevertheless, the mechanistic role of PHT in AS has not been fully clarified in relation to increased TSH. Therefore, in this review, we discuss the association between increased TSH and AS, and how increased TSH may be involved in the pathogenesis of AS. In addition, we also discuss how L-thyroxine treatment affects the development of AS.
PubMed: 38880884
DOI: 10.1186/s13044-024-00199-3 -
Neurointervention Jun 2024Delayed ischemic stroke associated with intractable vasospasm after clipping of unruptured intracranial aneurysms (UIAs) has been rarely reported. We report a patient...
Delayed ischemic stroke associated with intractable vasospasm after clipping of unruptured intracranial aneurysms (UIAs) has been rarely reported. We report a patient with delayed ischemic stroke associated with intractable vasospasm following UIA clipping. A middle-aged female underwent surgery for unruptured middle cerebral artery bifurcation aneurysms. The patient tolerated the neurosurgical procedure well. Seven days postoperatively, the headache was unbearable; a postcraniotomy headache persisted and abruptly presented with global aphasia and right-sided hemiplegia after a nap. Emergency digital subtraction angiography showed severe luminal narrowing with segmental vasoconstriction, consistent with severe vasospasm. The patient's neurological deficit improved after chemical angioplasty. Neurosurgeons should pay close attention to this treatable/preventive entity after neurological deterioration following UIA clipping, even in patients without subarachnoid hemorrhage.
PubMed: 38871004
DOI: 10.5469/neuroint.2024.00150 -
Revue Medicale de Liege Jun 2024Contrast-induced nephropathy (CIN) is a renal complication occurring after the administration of iodinated contrast agents routinely used in medical imaging. CIN causes... (Review)
Review
Contrast-induced nephropathy (CIN) is a renal complication occurring after the administration of iodinated contrast agents routinely used in medical imaging. CIN causes acute renal failure of varying severity. The pathophysiology of CIN is probably multifactorial: it involves (i) renal vasoconstriction inducing tissue hypoxia, and (ii) a possible direct toxicity of iodine derivatives leading to tubular inflammation and necrosis. Several risk factors are associated with CIN, some related to the procedure itself, others to the patient's co-morbid profile. In particular, the pre-existence of chronic renal failure, dehydration, congestive heart failure, diabetes or hypotension has been associated with an increased risk of CIN, as summarized in the Mehran score. Prevention of CIN relies essentially on adequate i.v. hydration before and after the procedure, and on the administration of the lowest possible volumes of contrast. In patients at high risk of CIN, the use of metformin and non-steroidal anti-inflammatory drugs is contraindicated at the time of contrast medium i.v. injection. In these patients, renal function assessment after 3-7 days post imaging is required.
Topics: Humans; Contrast Media; Kidney Diseases; Risk Factors; Acute Kidney Injury
PubMed: 38869133
DOI: No ID Found -
Bioscience Reports Jun 2024High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the...
High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to β-adrenergic receptor blockade but about forty percent of patients do not respond. Our aim was to use microarray to measure the expression of ~20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n = 12) versus healthy vessels (control, n = 9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted p value < 0.05, fold change > 1.5) identified 548 upregulated genes and 1,996 downregulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly upregulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly downregulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to β-blockers in patients with PH and cirrhosis.
PubMed: 38860875
DOI: 10.1042/BSR20240528