Biomedical subjects

Wenyan Li

Publications and source records attributed to Wenyan Li.

17 recordsLinked to original sources

PubMed2026

Acbd7 is essential for preserving hair cell-mediated auditory and vestibular function.

Understanding the molecular basis of hair cell function is essential for elucidating inner ear physiology and developing therapies for auditory-vestibular disorders. Here, we identify acyl-CoA binding domain-containing 7 (Acbd7) as a hair cell-specific gene critical for sensory maintenance. Single-cell transcriptomics of mouse cochlear organoids revealed Acbd7 as a top hair cell-enriched transcript, with its spatiotemporal expression confirmed from embryonic development through adulthood in both auditory and vestibular hair cells. Acbd7‑deficient mice exhibited pronounced hair cell degeneration, characterized by synaptic defects and diminished calcium currents in inner hair cells and loss of outer hair cells. Transcriptomic and proteomic analyses linked Acbd7 to the regulation of Ca2+ signaling and fatty acid metabolism pathways. Our findings establish Acbd7 as a critical regulator of Ca2+ homeostasis and functional integrity in hair cells, thereby elucidating a key mechanism by which a fatty acid metabolism factor sustains hair cell function and providing potential therapeutic targets for inner ear disorders.

Animals↗

PubMed2007

Somatic microindels: analysis in mouse soma and comparison with the human germline.

Microindels, defined as mutations that result in a colocalized microinsertion and microdeletion with a net gain or loss of between 1 and 50 nucleotides, may be an important contributor to cancer. We report the first comprehensive analysis of somatic microindels. Our large database of mutations in the lacI transgene of Big Blue((R)) mice contains 0.5% microindels, 2.8% pure microinsertions, and 11.5% pure microdeletions. There appears to be no age, gender, or tissue-type specificity in the frequency of microindels. Of the independent somatic mutations that result in a net in-frame insertion or deletion, microindels are responsible for 13% of protein expansions and 6% of protein contractions. These in-frame microindels may play a crucial role in oncogenesis and evolution via "protein tinkering" (i.e., modest expansion or contraction of proteins). Four characteristics suggest that microindels are caused by unique mechanisms, not just simple combinations of the same mechanisms that cause pure microinsertions and pure microdeletions. First, microinsertions and microdeletions commonly occur at hotspots, but none of the 30 microindels are recurrent. Second, the sizes of the deletions and insertions in microindels are larger and more varied than in pure microdeletions and pure microinsertions. Third, microinsertions overwhelmingly repeat the adjacent base (97%) while the insertions in microindels do so only infrequently (17%). Fourth, analysis of the sequence contexts of microindels is consistent with unique mechanisms including recruitment of translesion DNA synthesis polymerases. The mouse somatic microindels have characteristics similar to those of human germline microindels, consistent with similar causative mechanisms in mouse and human, and in soma and germline.

Age Factors↗

PubMed2006

Most spontaneous tumors in a mouse model of Li-Fraumeni syndrome do not have a mutator phenotype.

Mutations are the substrate of cancer. Yet, little is known about the degree and nature of mutations in tumors because measurement of mutation load in tumors and normal tissues was generally not possible until the advent of transgenic mouse mutation detection systems. Herein, we present the first analysis of mutation frequency and pattern in thymic tumors from a mouse model of Li-Fraumeni syndrome (p53+/- murine model) using the Big Blue assay with sequencing of all mutants. We also make the first characterization of mutation frequency and pattern in p53-deficient extra-thymic cancers. The data more than triple the literature on all non-mismatch repair deficient tumors for which mutations are identified by sequence analysis, allowing mutation frequency and pattern to be determined. Most tumors had a normal mutation frequency and a normal mutation pattern. Five tumors showed modest increases in mutation frequency (2.3-fold or less). Alterations in mutation patterns were uncommon, tumor-specific and not necessarily associated with increases in mutation frequency. Given the data from two spontaneous tumors (normal mutation frequency with an abnormal pattern in a p53-/- mouse and low mutation frequency in a p53+/+ control mouse), we hypothesize that tumors sometimes can carry a low mutation load. The study was not without certain caveats: mutation load could not be compared between tumor and normal tissue from the same animal; sample sizes for extra-thymic tumor types were small, and only point mutations and deletions, insertions and indels up to 2 kb were detected. However, the data clearly show key differences in tumors from p53+/- mice compared with mismatch repair deficient tumors; a lack of dramatic increase in mutation frequency and absence of a signature of mutation.

Animals↗

PubMed2006

Germ cell-less expression in zebrafish embryos.

The gene of germ cell-less (gcl) has been shown to be important in early differentiation of germ cells in Drosophila. Although the gcl homologue genes have been identified in some organisms, there is little data on the expression pattern and functional analysis of the gcl gene in zebrafish. In this research, real-time quantitative reverse transcription-polymerase chain reaction showed that the level of gcl mRNA expression rapidly decreases from the 4-cell stage to the sphere stage at which it reaches a minimum, gradually increases from the 50%-epiboly stage, and then remains stable during the posterior stages. Results of in situ hybridization indicated that the transcripts of zebrafish gcl are evenly distributed in all blastomeres from the 2-cell stage to the blastula period, different from that of vasa, nonas1 and dead end mRNA, and condense into some clusters of cells located along the blastoderm margin from the gastrulation period. During subsequent development, the transcripts are segregated as subcellular clumps to a small number of cells that would migrate to the position of the gonad in the dorsal side. In the adult, gcl mRNA was widely expressed in developing germ cells of both ovary and testis. These data suggest that zebrafish gcl have potentially important roles in the formation of primordial germ cells.

Animals↗

PubMed2005

Peroxynitrite-induced relaxation in isolated rat aortic rings and mechanisms of action.

The present study was designed to evaluate the effects of peroxynitrite (ONOO-), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOO- (from 10(-8) to 10(-4) M) failed to alter the basal tension. In phenylephrine (PE; 5 x 10(-7) M)-precontracted rat aortic rings (RAR), ONOO- elicited concentration-dependent relaxation at concentrations of from 10(-8) to 10(-4) M. The effective concentrations producing approximately 50% of maximal relaxation (ED50) to ONOO- were 1.84 x 10(-5) M and 1.96 x 10(-5) M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 microM methylene blue (MB) or 5 microM 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO-. Sildenafil (10(-7) M), on the other hand, significantly potentiated the ONOO--induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOO--induced relaxations in a concentration-dependent manner. However, ONOO- had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOO--induced relaxation in a dose-dependent manner. Furthermore, ONOO- significantly inhibited calcium-induced contractions of K+-depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOO- on RAR. Our new results suggest that ONOO--triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K+-channel activation, activation of myosin phosphatase activity, and interference with calcium movement and cellular membrane Ca2+ entry.

Animals↗

PubMed2005

Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases.

Intriguing parallels have been noted previously between the biology of Vitamin D and the epidemiology of schizophrenia. We have scanned the Vitamin D receptor (VDR) gene by DOVAM-S (Detection of Virtually All Mutations-SSCP), a robotically enhanced multiplexed scanning method. In total, 100 patients with schizophrenia (86 Caucasians and 14 African-Americans) were scanned. In addition, pilot experiments were performed in patients with bipolar disorder (BPD) (24), autism (24), attention deficit hyperactivity disorder (ADHD) (24), and alcoholism (20). A total of 762 kb of the VDR genomic sequence was scanned. R208N and V339I were each found in one African-American patient, while absent in 35 African-American controls without schizophrenia (2/14 versus 0/35, P=0.08). Within the power of the study (> or =1.6-fold relative risk), the common M1T variant is not associated with schizophrenia. In the 92 scanned patients with other psychiatric diseases, R173S was found in a single patient with bipolar disorder. In conclusion, we describe three novel structural variants of the Vitamin D receptor. Further study is required to clarify their role, if any, in psychiatric disease.

Amino Acid Sequence↗

PubMed2004

Mechanisms of hydroxyl radical-induced contraction of rat aorta.

The present study was designed to investigate the effects of hydroxyl radicals (*OH), generated via the Fe2+-mediated Fenton reaction, on isolated rat aortic rings with and without endothelium. In the absence of any vasoactive agent, generation of *OH alone elicited an endothelium-independent contraction in rat aortic rings in a concentration-dependent manner. Hydroxyl radical-induced contractions of denuded rat aortic rings appeared, however, to be slightly stronger than those on intact rat aortic rings. The contractile responses to *OH were neither reversible nor reproducible in the same ring; even small concentrations of *OH radicals resulted in tachyphylaxis. Removal of extracellular calcium ions (Ca2+) or buffering intracellular Ca2+ with 10 microM acetyl methyl ester of bis(o-aminophenoxy) ethane-N,N,N',N',-tetraacetic acid (BAPTA-AM) significantly attenuated the contractile actions of *OH radicals. The presence of 1 microM staurosporine, 1 microM bisindolylmaleimide I, 1 microM Gö6976 [inhibitor of protein kinase C (PKC)], 2 microM PD-980592 (inhibitor of ERK), 10 microM genistein, and 1 microM wortmannin significantly inhibited the contractions induced by *OH. Proadifen (10 microM), on the other hand, significantly potentiated the hydroxyl radical-induced contractions. Exposure of primary cultured aortic smooth muscle cells to *OH produced significant, rapid rises of intracellular free Ca2+ ([Ca2+]i). Several, specific antagonists of possible endogenously formed vasoconstrictors did not inhibit or attenuate either hydroxyl radical-induced contractions or the elevation of [Ca2+]i. Our new results suggest that hydroxyl radical-triggered contractions on rat aortic rings are Ca2+-dependent. Several intracellular signal transduction systems seem to play some role in hydroxyl radical-induced vasoconstriction of rat aortic rings.

Androstadienes↗

PubMed2004

Cocaine-induced relaxation of isolated rat aortic rings and mechanisms of action: possible relation to cocaine-induced aortic dissection and hypotension.

Cocaine HCl is well known for its toxic effects on the cardiovascular system, but little is known about its effects on different regional blood vessels. We designed experiments to determine if cocaine HCl could influence the tension of isolated aortic rings, i.e., induce contraction or relaxation. Surprisingly, cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) relaxed isolated aortic rings precontracted by phenylephrine in a concentration-dependent manner. No significant differences were found between intact or denuded isolated aortic rings (P>0.05). The maximal % relaxations of intact vs. denuded isolated aortic rings were 108.9+/-24.3% vs. 99.5+/-8.3% (P>0.05). Cocaine HCl, 2 x 10(-3) M, was found to inhibit contractions by phenylephrine; EC50s were increased (P<0.01) and Emax's were decreased (51.3+/-16.4% vs. 89.8+/-10.6%, P<0.01). A variety of amine antagonists could not inhibit the relaxant effects of cocaine HCl (P>0.05). The cyclooxygenase-1 inhibitor, indomethacin, also failed to inhibit relaxations induced by cocaine HCl (P>0.05). Neither L-arginine, NG-monomethyl-L-arginine (L-NMMA), nor methylene blue could inhibit the relaxations induced by cocaine HCl (P>0.05), suggesting cocaine HCl does not relax isolated aortic rings by inducing the synthesis or release of nitric oxide (NO) or prostanoids from either endothelial or vascular muscle cells. Inhibitors of cAMP, cGMP and protein kinase G (PKG) also failed to inhibit cocaine-induced relaxations. Cocaine HCl (1 x 10(-5) to 6 x 10(-3) M) could also relax isolated aortic rings precontracted by phenylephrine in high K+ depolarizing buffer. Surprisingly, calyculin A, an inhibitor of myosin light chain (MLC) phosphatase, inhibited cocaine-induced relaxations in a concentration-dependent manner, suggesting the probable importance of cocaine-induced MLC phosphatase activation in rat aortic smooth muscle cells. It was also found that cocaine HCl could dose-dependently inhibit Ca2+-induced contractions of isolated aortic rings in high K+-Ca2+-free buffer, suggesting that cocaine HCl may inhibit Ca2+ influx and/or intracellular release.

Aortic Dissection↗

PubMed2004

Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action.

The present study was undertaken to determine the vascular actions of peroxynitrite (ONOO(-)), the product of superoxide and nitric oxide (NO), in isolated canine cerebral arteries and to gain insight into its potential mechanisms of action. In the absence of any vasoactive agent, ONOO(-) (from 10(-7) to 10(-6) M) was able to reduce the basal tension. In prostaglandin F2alpha-precontracted canine basilar arterial rings, ONOO(-) elicited concentration-dependent relaxation at concentrations from 10(-8) to 10(-5) M. The effective concentrations producing approximately 50% maximal relaxation (EC(50)) to ONOO(-) were 4.06 x 10(-6) and 4.12 x 10(-6) M in intact and denuded rings, respectively (P > 0.05). No significant differences in relaxation responses were found in ring preparations with or without endothelium (P > 0.05). The presence of either 5 microM methylene blue (MB) or 5 microM 1H-[1,2,4]oxadiazolo-[4,3-alpha]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO(-). Tetraethylammonium chloride (T-2265) significantly decreased the ONOO(-)-induced relaxations in a concentration-dependent manner. However, ONOO(-) had no effect on rings precontracted by high KCL (P > 0.05). Addition of low concentrations of calyculin A (50 nM) was able to abolish the ONOO(-)-induced relaxation. Furthermore, ONOO(-) significantly inhibited calcium-induced contractions of K(+)-depolarized canine cerebral rings in a concentration-related manner. Lastly, a variety of pharmacological agents and antagonists including L-NMMA, l-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, etc., did not influence the relaxant effects of ONOO(-) on the rings. Our new results suggest that ONOO(-)-triggered relaxation, on canine cerebral arteries, is mediated by elevation of cyclic guanosine monophosphate (cGMP) levels, membrane hyperpolarization via K+ channel activation, activation of myosin light chain phosphatase activity, and interference with calcium movement and cellular membrane Ca(2+) entry.

Animals↗

PubMed2004

Alcohol-induced apoptosis of canine cerebral vascular smooth muscle cells: role of extracellular and intracellular calcium ions.

Exposure of canine cerebral vascular smooth muscle cells (VSMCs) to ethanol (10, 25 and 100 mM) for 1, 3 and 5 days induced apoptosis with its typical characteristics of nuclear shrinkage, condensation, and DNA breakage as well as formation of apoptotic bodies observed by fluorescence staining, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling and comet assays. Such effects of alcohol on cerebral VSMCs were time- and concentration-dependent. The threshold ethanol concentration for induction of the apoptotic process was found to be 10 mM. Extracellular and intracellular Ca2+ chelators, i.e. ethylglycol-bisbeta-aminoethylether-N,N,N'N'-tetraacetic acid (EGTA, 5 mM) and 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid AM (BAPTA, 10(-6) M), respectively, ameliorated greatly the number of cerebral VSMCs which underwent apoptosis. Verapamil, however, failed to inhibit apoptosis of cerebral VSMCs. From these new findings, we suggest that alcohol-induced apoptosis may contribute to alcohol-induced brain-vascular damage and stroke. In addition, our findings point to potential caution for humans who imbibe two or more standard drinks per day or who undergo 'binge drinking'.

Animals↗

PubMed2004

Peroxynitrite induces apoptosis in rat aortic smooth muscle cells: possible relation to vascular diseases.

An emerging body of evidence is accumulating to suggest that in vivo formation of free radicals in the vasculature, such as peroxynitrite (ONOO-), and programmed cell death (i.e., apoptosis) play important roles in vascular diseases such as atherosclerosis, hypertension, and restenosis. The present study was designed to determine whether primary rat aortic smooth muscle cells (SMCs) undergo apoptosis following treatment with ONOO-. Direct exposure of primary rat aortic SMCs to ONOO--induced apoptosis in a concentration-dependent manner, as confirmed by means of quantitative fluorescence staining and TUNEL assays. ONOO--induced apoptosis in rat aortic SMCs appears to involve activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis in rat aortic SMCs need to be further investigated, the present, preliminary findings could be used to suggest that ONOO- formation in the vasculature may play roles in the processes of vascular diseases, such as atherosclerosis, hypertension, and restenosis, via adverse actions on blood vessels.

Animals↗

PubMed2003

Hydrogen peroxide induces apoptosis in cerebral vascular smooth muscle cells: possible relation to neurodegenerative diseases and strokes.

Recently, reactive oxygen species (ROS) have been suggested as important mediators of brain damage in a number of disease states, including traumatic brain injury, neurodegenerative diseases and strokes. Apoptosis has been suggested to play an important role in neurodegenerative diseases, traumatic brain injury and strokes. The aim of this study was to determine whether or not cerebral vascular smooth muscle cells (CVSMCs) undergo apoptosis following treatment with hydrogen peroxide (H2O2). Herein, we demonstrate, for the first time, that H2O2 can induce apoptosis in a concentration-dependent manner in primary cultured CVSMCs, as measured by several morphological and biochemical criteria. H2O2-induced apoptosis may be initiated by stimulating Ca2+-dependent endonuclease activity. The present new data suggest that apoptosis in cerebral VSMCs, induced by ROS, such as H2O2, could play important roles in neruodegenerative processes, traumatic brain injury and strokes.

Animals↗

PubMed2003

Cocaine induces apoptosis in cerebral vascular muscle cells: potential roles in strokes and brain damage.

Cocaine abuse is known to induce different types of brain-microvascular damage and many adverse cerebrovascular effects, including cerebral vasculitis, intracranial hemorrhage, cerebral infarction and stroke. A major physiological event leading to these pathophysiological actions of cocaine could be apoptosis. Whether cocaine can cause brain-microvascular pathology and vascular toxicity by inducing apoptosis of cerebral vascular smooth muscle cells is not known. This study, using several different methods to discern apoptosis, was designed to investigate if primary cultured canine cerebral vascular smooth muscle cells can undergo apoptosis when treated with cocaine. After treatment with cocaine (10(-6)-10(-3) M) for 12-24 h, the death rates of cerebral vascular smooth muscle cells increased in a concentration-dependent manner compared with controls. Morphological analysis of cerebral vascular smooth muscle cells using confocal fluoresence microscopy showed that the percentage of apoptotic cerebral vascular smooth muscle cells increased after cocaine (10(-6)-10(-3) M) treatment in a concentration-dependent manner. TUNEL assays also showed positive results for cerebral vascular smooth muscle cells treated with cocaine. These results clearly demonstrate that cerebral vascular smooth muscle cells can undergo rapid apoptosis in response to cocaine in a concentration-dependent manner. Cocaine-induced apoptosis may thus play a major role in brain-microvascular damage, cerebral vascular toxicity and strokes.

Animals↗

PubMed2003

Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes.

Considerable evidence is accumulating to suggest that in vivo formation of free radicals in the brain, such as peroxynitrite (ONOO-), and programmed cell death (i.e. apoptosis) play important roles in neurodegeneration and stroke. However, it is not known whether ONOO- can induce apoptosis in cerebral vascular smooth muscle cells (CVSMCs). The present study was designed to determine whether or not canine CVSMCs undergo apoptosis following treatment with ONOO-. Direct exposure of canine CVSMCs to ONOO- induced apoptosis in a concentration-dependent manner, as confirmed by means of fluorescence staining, TdT-mediated dUTP nick-end labeling and comet assays. Peroxynitrite treatment resulted in an elevation of [Ca2+]i in the CVSMCs. Peroxynitrite-induced apoptosis may thus be brought about by activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis need to be further investigated, the present findings could be used to suggest that ONOO- formation in the brain may play important roles in neurodegenerative processes and strokes via detrimental actions on cerebral microvessels and blood flow.

Animals↗

PubMed2003

Catalase prevents elevation of [Ca(2+)](i) induced by alcohol in cultured canine cerebral vascular smooth muscle cells: Possible relationship to alcohol-induced stroke and brain pathology.

Several studies have suggested that alcohol-induced brain injury is associated with generation of reactive oxygen species (ROS). The recent findings, that antioxidants (Vitamin E and pyrrolidine dithiocarbamate (PDTC)) prevent intracellular Ca(2+) ([Ca(2+)](i)) overload in cerebral vascular smooth muscle cells, induced by alcohol, demonstrate indirectly that ROS formation is related to cerebral vascular injury. The present experiments were designed to test the hypothesis that catalase, an hydrogen peroxide (H(2)O(2)) scavenging enzyme, can prevent or ameliorate alcohol-induced elevation of [Ca(2+)](i). Preincubation of cultured canine cerebral vascular smooth muscle cells with catalase (20-1000 units/ml) didn't produce any apparent changes from controls in resting levels of [Ca(2+)](i) after 1-3 days. Exposure of the cerebral vascular cells to culture media containing 10-100mM ethanol resulted in significant rises in [Ca(2+)](i) (p<0.01). Although exposure of these cells to a low concentration of catalase (20 units/ml) failed to prevent the increased level of [Ca(2+)](i) induced by ethanol, concomitant addition of higher concentrations of catalase (100-1000 units/ml) and ethanol (10-100mM) inhibited or ameliorated the rises of [Ca(2+)](i) induced by ethanol either at 24h or at 3 days, in a concentration-dependent manner. Catalase, in the range of 100-200 units/ml, inhibited approximately 50% of the [Ca(2+)](i) increases caused by ethanol in the first 24h. Catalase at a concentration of 1000 units/ml inhibited completely excessive [Ca(2+)](i) accumulation. The present results when viewed in light of other recently published data suggest that H(2)O(2) generation may be one of the earliest events triggered by alcohol in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.

Animals↗

PubMed2003

Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke.

Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.

Animals↗

PubMedDate not supplied

Cocaine induces apoptosis in primary cultured rat aortic vascular smooth muscle cells: possible relationship to aortic dissection, atherosclerosis, and hypertension.

Cocaine abuse is known to induce many adverse cardiovascular effects, including hypertension, atherosclerosis, and aortic dissection. A major physiological event leading to these pathophysiological actions of cocaine could be apoptosis. This study was designed to investigate if primary cultured rat aortic vascular smooth muscle cells (VSMCs) can undergo apoptosis when treated with cocaine. After treatment with cocaine (10(-6) to 10(-4) M), morphological analysis of aortic VSMCs using confocal fluoresence microscopy showed that the percentage of apoptotic aortic VSMCs increased after cocaine (10(-6) to 10(-4) M) treatment for 12, 24, and 48 h. These results demonstrate that aortic VSMCs can undergo rapid apoptosis in response to cocaine in a concentration-dependent manner. Cocaine-induced apoptosis may thus play a major role in cocaine abuse-induced aortic dissection, atherosclerosis, and hypertension.

Animals↗